Engineered Tumor-Targeted T Cells Mediate Enhanced Anti-Tumor Efficacy Both Directly and through Activation of the Endogenous Immune System

Chimeric antigen receptor (CAR) T cell therapy has proven clinically beneficial against B cell acute lymphoblastic leukemia and non-Hodgkin’s lymphoma. However, suboptimal clinical outcomes have been associated with decreased expansion and persistence of adoptively transferred CAR T cells, antigen-n...

Full description

Saved in:

Bibliographic Details
Published in:	Cell reports (Cambridge) Vol. 23; no. 7; pp. 2130 - 2141
Main Authors:	Avanzi, Mauro P., Yeku, Oladapo, Li, Xinghuo, Wijewarnasuriya, Dinali P., van Leeuwen, Dayenne G., Cheung, Kenneth, Park, Hyebin, Purdon, Terence J., Daniyan, Anthony F., Spitzer, Matthew H., Brentjens, Renier J.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 15.05.2018
Subjects:	adoptive transfer Animals Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use armored CAR Autocrine Communication - drug effects B-ALL B-Lymphocytes - drug effects CAR T cell Cell Proliferation - drug effects Cell Survival - drug effects chimeric antigen receptor Disease Models, Animal Humans IL-18 Immune System - drug effects Immune System - metabolism Immunotherapy Immunotherapy, Adoptive interleukin-18 Interleukin-18 - metabolism Mice, Inbred C57BL Mice, SCID MUC16 Neoplasms - drug therapy Neoplasms - immunology Neoplasms - pathology ovarian cancer Signal Transduction - drug effects T-Lymphocytes - drug effects T-Lymphocytes - immunology Tumor Microenvironment - drug effects Xenograft Model Antitumor Assays armored CAR B-ALL MUC16 interleukin-18 ovarian cancer IL-18 chimeric antigen receptor adoptive transfer CAR T cell
ISSN:	2211-1247, 2211-1247
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Abstract	Chimeric antigen receptor (CAR) T cell therapy has proven clinically beneficial against B cell acute lymphoblastic leukemia and non-Hodgkin’s lymphoma. However, suboptimal clinical outcomes have been associated with decreased expansion and persistence of adoptively transferred CAR T cells, antigen-negative relapses, and impairment by an immunosuppressive tumor microenvironment. Improvements in CAR T cell design are required to enhance clinical efficacy, as well as broaden the applicability of this technology. Here, we demonstrate that interleukin-18 (IL-18)-secreting CAR T cells exhibit enhanced in vivo expansion and persistence and significantly increase long-term survival in syngeneic mouse models of both hematological and solid malignancies. In addition, we demonstrate that IL-18-secreting CAR T cells are capable of modulating the tumor microenvironment, as well as enhancing an effective endogenous anti-tumor immune response. IL-18-secreting CAR T cells represent a promising strategy to enhance the clinical outcomes of adoptive T cell therapy. [Display omitted] •IL-18-secreting CAR T cells enhance anti-tumor efficacy via IL-18 autocrine stimulation•IL-18-secreting CAR T cells favorably alter EL4 tumor microenvironment•IL-18-secreting CAR T cells enhance the anti-tumor response of endogenous T cells•IL-18-secreting CAR T cells are efficacious in syngeneic models without preconditioning Avanzi et al. generate CAR T cells that secrete IL-18 and show improved activity in syngeneic hematologic and solid tumor models without prior preconditioning. They further show enhanced recruitment and anti-tumor activity of endogenous T cells.
AbstractList	Chimeric antigen receptor (CAR) T cell therapy has proven clinically beneficial against B cell acute lymphoblastic leukemia and non-Hodgkin's lymphoma. However, suboptimal clinical outcomes have been associated with decreased expansion and persistence of adoptively transferred CAR T cells, antigen-negative relapses, and impairment by an immunosuppressive tumor microenvironment. Improvements in CAR T cell design are required to enhance clinical efficacy, as well as broaden the applicability of this technology. Here, we demonstrate that interleukin-18 (IL-18)-secreting CAR T cells exhibit enhanced in vivo expansion and persistence and significantly increase long-term survival in syngeneic mouse models of both hematological and solid malignancies. In addition, we demonstrate that IL-18-secreting CAR T cells are capable of modulating the tumor microenvironment, as well as enhancing an effective endogenous anti-tumor immune response. IL-18-secreting CAR T cells represent a promising strategy to enhance the clinical outcomes of adoptive T cell therapy.Chimeric antigen receptor (CAR) T cell therapy has proven clinically beneficial against B cell acute lymphoblastic leukemia and non-Hodgkin's lymphoma. However, suboptimal clinical outcomes have been associated with decreased expansion and persistence of adoptively transferred CAR T cells, antigen-negative relapses, and impairment by an immunosuppressive tumor microenvironment. Improvements in CAR T cell design are required to enhance clinical efficacy, as well as broaden the applicability of this technology. Here, we demonstrate that interleukin-18 (IL-18)-secreting CAR T cells exhibit enhanced in vivo expansion and persistence and significantly increase long-term survival in syngeneic mouse models of both hematological and solid malignancies. In addition, we demonstrate that IL-18-secreting CAR T cells are capable of modulating the tumor microenvironment, as well as enhancing an effective endogenous anti-tumor immune response. IL-18-secreting CAR T cells represent a promising strategy to enhance the clinical outcomes of adoptive T cell therapy. Chimeric antigen receptor (CAR) T cell therapy has proven clinically beneficial against B cell acute lymphoblastic leukemia and non-Hodgkin’s lymphoma. However, suboptimal clinical outcomes have been associated with decreased expansion and persistence of adoptively transferred CAR T cells, antigen-negative relapses, and impairment by an immunosuppressive tumor microenvironment. Improvements in CAR T cell design are required to enhance clinical efficacy, as well as broaden the applicability of this technology. Here, we demonstrate that interleukin-18 (IL-18)-secreting CAR T cells exhibit enhanced in vivo expansion and persistence and significantly increase long-term survival in syngeneic mouse models of both hematological and solid malignancies. In addition, we demonstrate that IL-18-secreting CAR T cells are capable of modulating the tumor microenvironment, as well as enhancing an effective endogenous anti-tumor immune response. IL-18-secreting CAR T cells represent a promising strategy to enhance the clinical outcomes of adoptive T cell therapy. [Display omitted] •IL-18-secreting CAR T cells enhance anti-tumor efficacy via IL-18 autocrine stimulation•IL-18-secreting CAR T cells favorably alter EL4 tumor microenvironment•IL-18-secreting CAR T cells enhance the anti-tumor response of endogenous T cells•IL-18-secreting CAR T cells are efficacious in syngeneic models without preconditioning Avanzi et al. generate CAR T cells that secrete IL-18 and show improved activity in syngeneic hematologic and solid tumor models without prior preconditioning. They further show enhanced recruitment and anti-tumor activity of endogenous T cells. Chimeric antigen receptor (CAR) T cell therapy has proven clinically beneficial against B cell acute lymphoblastic leukemia and non-Hodgkin’s lymphoma. However, suboptimal clinical outcomes have been associated with decreased expansion and persistence of adoptively transferred CAR T cells, antigen-negative relapses, and impairment by an immunosuppressive tumor microenvironment. Improvements in CAR T cell design are required to enhance clinical efficacy, as well as broaden the applicability of this technology. Here, we demonstrate that interleukin-18 (IL-18)-secreting CAR T cells exhibit enhanced in vivo expansion and persistence and significantly increase long-term survival in syngeneic mouse models of both hematological and solid malignancies. In addition, we demonstrate that IL-18-secreting CAR T cells are capable of modulating the tumor microenvironment, as well as enhancing an effective endogenous anti-tumor immune response. IL-18-secreting CART cells represent a promising strategy to enhance the clinical outcomes of adoptive T cell therapy. In Brief Avanzi et al. generate CAR T cells that secrete IL-18 and show improved activity in syngeneic hematologic and solid tumor models without prior preconditioning. They further show enhanced recruitment and anti-tumor activity of endogenous T cells. Chimeric antigen receptor (CAR) T cell therapy has proven clinically beneficial against B cell acute lymphoblastic leukemia and non-Hodgkin's lymphoma. However, suboptimal clinical outcomes have been associated with decreased expansion and persistence of adoptively transferred CAR T cells, antigen-negative relapses, and impairment by an immunosuppressive tumor microenvironment. Improvements in CAR T cell design are required to enhance clinical efficacy, as well as broaden the applicability of this technology. Here, we demonstrate that interleukin-18 (IL-18)-secreting CAR T cells exhibit enhanced in vivo expansion and persistence and significantly increase long-term survival in syngeneic mouse models of both hematological and solid malignancies. In addition, we demonstrate that IL-18-secreting CAR T cells are capable of modulating the tumor microenvironment, as well as enhancing an effective endogenous anti-tumor immune response. IL-18-secreting CAR T cells represent a promising strategy to enhance the clinical outcomes of adoptive T cell therapy.
Author	Daniyan, Anthony F. Brentjens, Renier J. Purdon, Terence J. Yeku, Oladapo van Leeuwen, Dayenne G. Avanzi, Mauro P. Li, Xinghuo Wijewarnasuriya, Dinali P. Park, Hyebin Cheung, Kenneth Spitzer, Matthew H.
AuthorAffiliation	3 Weill Cornell School of Medicine, New York, NY, USA 1 Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA 2 Department of Microbiology and Immunology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA
AuthorAffiliation_xml	– name: 1 Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA – name: 2 Department of Microbiology and Immunology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA – name: 3 Weill Cornell School of Medicine, New York, NY, USA
Author_xml	– sequence: 1 givenname: Mauro P. surname: Avanzi fullname: Avanzi, Mauro P. organization: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA – sequence: 2 givenname: Oladapo surname: Yeku fullname: Yeku, Oladapo email: yekuo@mskcc.org organization: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA – sequence: 3 givenname: Xinghuo surname: Li fullname: Li, Xinghuo organization: Weill Cornell School of Medicine, New York, NY, USA – sequence: 4 givenname: Dinali P. surname: Wijewarnasuriya fullname: Wijewarnasuriya, Dinali P. organization: Weill Cornell School of Medicine, New York, NY, USA – sequence: 5 givenname: Dayenne G. surname: van Leeuwen fullname: van Leeuwen, Dayenne G. organization: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA – sequence: 6 givenname: Kenneth surname: Cheung fullname: Cheung, Kenneth organization: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA – sequence: 7 givenname: Hyebin surname: Park fullname: Park, Hyebin organization: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA – sequence: 8 givenname: Terence J. surname: Purdon fullname: Purdon, Terence J. organization: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA – sequence: 9 givenname: Anthony F. surname: Daniyan fullname: Daniyan, Anthony F. organization: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA – sequence: 10 givenname: Matthew H. surname: Spitzer fullname: Spitzer, Matthew H. organization: Department of Microbiology and Immunology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA – sequence: 11 givenname: Renier J. surname: Brentjens fullname: Brentjens, Renier J. email: brentjer@mskcc.org organization: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/29768210$$D View this record in MEDLINE/PubMed
BookMark	eNqFkcGO0zAQhi20iF2WfQOEfOSSYHsTJ-GAVEqBlRZxoJwt154krhK72E6lPgMvjdN20cIBfLFn5p9_5PmeowvrLCD0kpKcEsrfbHMFg4ddzgitc1LkpKRP0BVjlGaUFdXFo_cluglhS9LhhNKmeIYuWVPxmlFyhX6ubGcsgAeN19PofLaWvoM4h3gJwxDwF9BGRsAr20urUmFho8mOYrxqW6OkOuD3Lvb4g_Gg4nDA0moce--mrscLFc1eRuMsdm3KzkbadWDdFPDdOE4W8LdDiDC-QE9bOQS4Od_X6PvH1Xr5Obv_-uluubjPVMFvY8ZlLTdKq7qkDVDVtA2tN1wXFYdGSU3LlGDAJZNtKeu2gQ0lKUcqTloADrfX6N3JdzdtRtAKbPRyEDtvRukPwkkj_qxY04vO7UXZ1JzVPBm8Pht492OCEMVoQgIySAvpV4KRglRlWfImSV89nvV7yAOBJHh7EijvQvDQCmXicV1ptBkEJWImLrbiRFzMxAUpRCKemou_mh_8_9N2XgCkLe8NeBGUgZntEaDQzvzb4Bev9MqE
CitedBy_id	crossref_primary_10_3390_biom11020238 crossref_primary_10_1136_jitc_2020_001053 crossref_primary_10_3390_cancers12082030 crossref_primary_10_1038_s41587_023_02060_8 crossref_primary_10_1080_1354750X_2021_2016973 crossref_primary_10_1038_s41375_020_0874_1 crossref_primary_10_1016_j_semcancer_2022_05_002 crossref_primary_10_3324_haematol_2023_283817 crossref_primary_10_1097_PPO_0000000000000510 crossref_primary_10_1016_j_cytogfr_2020_07_007 crossref_primary_10_3390_cancers13236000 crossref_primary_10_3390_cancers13133236 crossref_primary_10_3390_cancers13225592 crossref_primary_10_3389_fimmu_2023_1063454 crossref_primary_10_1016_j_canlet_2022_215949 crossref_primary_10_1016_j_prp_2025_156036 crossref_primary_10_3389_fimmu_2023_1062365 crossref_primary_10_2147_BTT_S291768 crossref_primary_10_1186_s12943_022_01712_8 crossref_primary_10_1016_j_copbio_2023_103020 crossref_primary_10_3389_fonc_2019_00069 crossref_primary_10_3390_cancers12051075 crossref_primary_10_3389_fimmu_2022_927153 crossref_primary_10_1158_2326_6066_CIR_21_0253 crossref_primary_10_1002_cpt_1280 crossref_primary_10_1126_sciimmunol_abd4344 crossref_primary_10_1136_jitc_2022_006292 crossref_primary_10_1182_blood_2023022293 crossref_primary_10_1002_mog2_40 crossref_primary_10_1186_s13045_023_01492_8 crossref_primary_10_1038_nbt_4195 crossref_primary_10_1158_1078_0432_CCR_21_2681 crossref_primary_10_1016_j_copbio_2020_01_009 crossref_primary_10_1016_j_ccell_2020_07_005 crossref_primary_10_1136_jitc_2021_003737 crossref_primary_10_1038_s41586_022_04801_2 crossref_primary_10_1007_s12026_021_09236_x crossref_primary_10_1080_14712598_2019_1614164 crossref_primary_10_1172_JCI129206 crossref_primary_10_1016_j_lungcan_2021_05_004 crossref_primary_10_1002_EXP_20210058 crossref_primary_10_1038_s41590_020_0676_7 crossref_primary_10_1097_CCO_0000000000000671 crossref_primary_10_3389_fimmu_2021_717850 crossref_primary_10_3389_fimmu_2023_1114770 crossref_primary_10_1038_s41467_019_13088_3 crossref_primary_10_1111_imr_13252 crossref_primary_10_1186_s40364_022_00434_9 crossref_primary_10_1016_j_ymthe_2023_09_021 crossref_primary_10_1080_08820139_2022_2096463 crossref_primary_10_1038_s41589_021_00932_1 crossref_primary_10_3389_fphar_2025_1493346 crossref_primary_10_1016_j_bbmt_2019_02_008 crossref_primary_10_3389_fimmu_2020_589381 crossref_primary_10_1016_j_it_2018_10_003 crossref_primary_10_3390_jpm13111595 crossref_primary_10_1097_CCO_0000000000000562 crossref_primary_10_1186_s40425_019_0741_7 crossref_primary_10_1038_s41587_024_02446_2 crossref_primary_10_1016_j_jconrel_2019_12_047 crossref_primary_10_1186_s12943_024_02047_2 crossref_primary_10_1038_s41573_023_00807_1 crossref_primary_10_1111_nyas_14526 crossref_primary_10_1038_s41392_023_01680_5 crossref_primary_10_1158_2326_6066_CIR_24_0975 crossref_primary_10_1007_s11912_023_01443_z crossref_primary_10_1016_j_omto_2022_03_009 crossref_primary_10_3389_fimmu_2022_887471 crossref_primary_10_1097_CCO_0000000000000653 crossref_primary_10_1016_j_nantod_2022_101621 crossref_primary_10_1016_j_trecan_2025_06_008 crossref_primary_10_3390_cancers14092177 crossref_primary_10_1002_ctm2_1141 crossref_primary_10_1038_s41587_019_0398_2 crossref_primary_10_1016_j_hoc_2023_05_009 crossref_primary_10_1038_s41375_020_0951_5 crossref_primary_10_1111_ejh_14074 crossref_primary_10_1080_15592294_2023_2265625 crossref_primary_10_3389_fped_2021_784024 crossref_primary_10_3390_ijms21228655 crossref_primary_10_3389_fimmu_2022_830292 crossref_primary_10_1080_1744666X_2024_2380894 crossref_primary_10_3390_ijms252212201 crossref_primary_10_3390_ijms242115688 crossref_primary_10_1016_j_pan_2020_02_006 crossref_primary_10_1186_s12920_019_0489_4 crossref_primary_10_3389_fimmu_2024_1489827 crossref_primary_10_1182_blood_2024024063 crossref_primary_10_1007_s40265_022_01702_6 crossref_primary_10_1186_s13045_024_01625_7 crossref_primary_10_3389_fimmu_2022_1090959 crossref_primary_10_1177_2399369319863433 crossref_primary_10_1002_pbc_28313 crossref_primary_10_1016_j_cell_2020_03_001 crossref_primary_10_1016_j_xcrm_2025_102353 crossref_primary_10_3389_fimmu_2024_1465191 crossref_primary_10_1136_jitc_2024_010545 crossref_primary_10_3389_fimmu_2024_1509956 crossref_primary_10_1007_s11684_020_0746_0 crossref_primary_10_1038_s41573_019_0051_2 crossref_primary_10_3389_fimmu_2022_984864 crossref_primary_10_3390_ijms22020640 crossref_primary_10_1016_j_jcyt_2025_05_010 crossref_primary_10_1002_ptr_6784 crossref_primary_10_3390_cancers16122270 crossref_primary_10_1007_s13760_024_02519_8 crossref_primary_10_3390_ijms231911526 crossref_primary_10_3390_cancers16183186 crossref_primary_10_1080_17474086_2020_1753501 crossref_primary_10_3390_mps8050108 crossref_primary_10_1097_MOH_0000000000000614 crossref_primary_10_3390_cancers12020375 crossref_primary_10_1084_jem_20192203 crossref_primary_10_1016_j_canlet_2025_217771 crossref_primary_10_1126_scitranslmed_adh1150 crossref_primary_10_1002_adhm_202002214 crossref_primary_10_3389_fimmu_2022_907022 crossref_primary_10_3390_ijms252312992 crossref_primary_10_1038_s41571_019_0184_6 crossref_primary_10_3390_cancers15061650 crossref_primary_10_1186_s13045_021_01209_9 crossref_primary_10_3892_ijo_2024_5628 crossref_primary_10_1016_j_biomaterials_2019_119265 crossref_primary_10_3389_fimmu_2021_782775 crossref_primary_10_1007_s11596_021_2391_5 crossref_primary_10_1182_blood_2020009515 crossref_primary_10_1002_cyto_a_24158 crossref_primary_10_1038_s41551_022_00875_5 crossref_primary_10_1038_s41586_023_05707_3 crossref_primary_10_3390_ijms232314563 crossref_primary_10_1002_acg2_72 crossref_primary_10_1016_j_cmet_2024_12_007 crossref_primary_10_1038_s41423_020_00555_x crossref_primary_10_1080_1750743X_2025_2536458 crossref_primary_10_1126_scitranslmed_ado9371 crossref_primary_10_1002_hon_2591 crossref_primary_10_1007_s00262_025_04001_7 crossref_primary_10_1002_cpt_1674 crossref_primary_10_1155_2021_6644685 crossref_primary_10_1016_j_coi_2021_02_010 crossref_primary_10_1038_s41571_023_00729_2 crossref_primary_10_1080_1061186X_2022_2032095 crossref_primary_10_3389_fphar_2021_720692 crossref_primary_10_3389_fonc_2023_1275076 crossref_primary_10_3389_fimmu_2022_867154 crossref_primary_10_1007_s11427_019_9665_8 crossref_primary_10_1007_s10555_019_09821_5 crossref_primary_10_1016_j_addr_2021_114032 crossref_primary_10_1186_s40364_022_00391_3 crossref_primary_10_1038_s41467_022_28243_6 crossref_primary_10_3389_fimmu_2025_1643941 crossref_primary_10_1016_j_ymthe_2020_09_015 crossref_primary_10_1080_14737140_2024_2421194 crossref_primary_10_1016_j_beha_2021_101304 crossref_primary_10_1016_j_blre_2024_101241 crossref_primary_10_1080_13543784_2023_2230137 crossref_primary_10_1186_s13045_020_00947_6 crossref_primary_10_1002_ajh_25416 crossref_primary_10_1158_2326_6066_CIR_21_0536 crossref_primary_10_3389_fimmu_2021_684642 crossref_primary_10_1136_jitc_2025_011761 crossref_primary_10_1038_s41417_023_00642_x crossref_primary_10_3389_fimmu_2023_1303935 crossref_primary_10_1186_s12967_023_04117_3 crossref_primary_10_1172_JCI166028 crossref_primary_10_1084_jem_20190589 crossref_primary_10_1136_jitc_2020_001544 crossref_primary_10_1016_j_jconrel_2024_02_033 crossref_primary_10_1158_2326_6066_CIR_19_0908 crossref_primary_10_3389_fimmu_2022_850358 crossref_primary_10_3389_fimmu_2021_652160 crossref_primary_10_3390_ijms24119115 crossref_primary_10_1002_acg2_84 crossref_primary_10_1038_s41573_021_00189_2 crossref_primary_10_1080_1750743X_2024_2408048 crossref_primary_10_1158_2326_6066_CIR_19_0910 crossref_primary_10_3389_fimmu_2023_1165870 crossref_primary_10_1038_nbt_4215 crossref_primary_10_1016_j_tmrv_2019_08_003 crossref_primary_10_1158_1078_0432_CCR_23_3157 crossref_primary_10_1038_s41568_020_00323_z crossref_primary_10_1080_14712598_2021_1857361 crossref_primary_10_1016_j_addr_2020_07_015 crossref_primary_10_1002_INMD_20230047 crossref_primary_10_3389_fimmu_2021_738456 crossref_primary_10_1016_j_molmed_2023_01_006 crossref_primary_10_1016_j_ymthe_2024_06_022 crossref_primary_10_1038_s41571_019_0297_y crossref_primary_10_1136_jitc_2021_003679 crossref_primary_10_1158_2159_8290_CD_20_1661 crossref_primary_10_1016_j_coph_2021_05_005 crossref_primary_10_1016_S0007_4551_19_30048_7 crossref_primary_10_1056_NEJMoa2408771 crossref_primary_10_3390_cells10112940 crossref_primary_10_1016_j_medj_2022_05_001 crossref_primary_10_3390_ph17121629 crossref_primary_10_1002_smll_202506429 crossref_primary_10_1016_j_prp_2025_155947 crossref_primary_10_1007_s11912_021_01161_4 crossref_primary_10_1186_s13045_021_01083_5 crossref_primary_10_3390_cancers14051241 crossref_primary_10_1016_j_biotechadv_2019_06_010 crossref_primary_10_1038_s41586_025_09212_7 crossref_primary_10_3389_fonc_2019_00146 crossref_primary_10_1038_s41591_018_0212_6 crossref_primary_10_1096_fj_201901809R crossref_primary_10_1158_1535_7163_MCT_24_0597 crossref_primary_10_1186_s12967_025_06857_w crossref_primary_10_1016_j_jcis_2022_03_084 crossref_primary_10_1016_j_ymthe_2025_02_029 crossref_primary_10_1186_s12943_025_02334_6 crossref_primary_10_3390_ijms21218000 crossref_primary_10_1016_j_jtct_2024_04_004 crossref_primary_10_1097_BS9_0000000000000025 crossref_primary_10_3389_fimmu_2021_816658 crossref_primary_10_1158_1078_0432_CCR_21_1559 crossref_primary_10_1111_imr_12920 crossref_primary_10_1016_j_apmt_2021_101255 crossref_primary_10_1007_s40265_019_01071_7 crossref_primary_10_1002_jcp_27425 crossref_primary_10_1093_abt_tbac006 crossref_primary_10_1016_j_ymthe_2018_09_008 crossref_primary_10_3390_cancers13040598 crossref_primary_10_1097_COC_0000000000000669 crossref_primary_10_1016_j_omtn_2024_102308 crossref_primary_10_3389_fimmu_2021_681984 crossref_primary_10_3389_fimmu_2022_795164 crossref_primary_10_3389_fmed_2024_1462307 crossref_primary_10_3390_biomedicines10092286 crossref_primary_10_3390_cancers13215367 crossref_primary_10_3390_ijms23063154 crossref_primary_10_1007_s00281_022_00962_4 crossref_primary_10_3389_fimmu_2025_1564998 crossref_primary_10_1007_s13577_024_01066_x crossref_primary_10_1146_annurev_cancerbio_061421_012235 crossref_primary_10_1016_j_ccell_2019_02_006 crossref_primary_10_1016_j_ymthe_2024_05_013
Cites_doi	10.1182/blood-2011-05-354449 10.1038/nrclinonc.2016.36 10.1158/1078-0432.CCR-13-0458 10.1182/blood-2017-02-769208 10.1038/mt.2014.164 10.1186/s13045-016-0378-7 10.4161/2162402X.2014.994446 10.1038/sj.neo.7900018 10.1126/science.1259425 10.1126/scitranslmed.3008226 10.1016/j.celrep.2017.11.063 10.1016/j.celrep.2017.09.002 10.1158/1078-0432.CCR-07-0674 10.1182/blood-2011-12-400044 10.1182/blood-2005-11-4535 10.1056/NEJMoa1407222 10.1158/1078-0432.CCR-10-0192 10.3389/fimmu.2011.00029 10.1038/leu.2014.215 10.1038/srep14273 10.1182/blood-2013-07-517219 10.1016/S0140-6736(14)61403-3 10.18632/oncotarget.3597 10.1158/2159-8290.CD-15-1020 10.1038/nprot.2015.020 10.1111/j.1600-065X.2006.00442.x 10.1172/JCI83092 10.1016/S1471-4906(02)02302-5 10.1056/NEJMoa1610497 10.1126/scitranslmed.aaa0984 10.1182/blood-2015-08-665547 10.1126/scitranslmed.3002842 10.1126/scitranslmed.3005930 10.1038/nm827
ContentType	Journal Article
Copyright	2018 The Authors Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
Copyright_xml	– notice: 2018 The Authors – notice: Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
DBID	6I. AAFTH AAYXX CITATION CGR CUY CVF ECM EIF NPM 7X8 5PM
DOI	10.1016/j.celrep.2018.04.051
DatabaseName	ScienceDirect Open Access Titles Elsevier:ScienceDirect:Open Access CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic PubMed Central (Full Participant titles)
DatabaseTitle	CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic
DatabaseTitleList	MEDLINE - Academic MEDLINE
Database_xml	– sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database
DeliveryMethod	fulltext_linktorsrc
Discipline	Biology
EISSN	2211-1247
EndPage	2141
ExternalDocumentID	PMC5986286 29768210 10_1016_j_celrep_2018_04_051 S2211124718306107
Genre	Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural
GrantInformation_xml	– fundername: NCI NIH HHS grantid: R25 CA020449 – fundername: NCI NIH HHS grantid: P50 CA192937 – fundername: NCI NIH HHS grantid: P01 CA023766 – fundername: NCI NIH HHS grantid: T32 CA009207 – fundername: NIH HHS grantid: DP5 OD023056 – fundername: NCI NIH HHS grantid: P30 CA008748 – fundername: NCI NIH HHS grantid: P01 CA190174 – fundername: NCI NIH HHS grantid: P01 CA059350 – fundername: NCI NIH HHS grantid: K12 CA184746 – fundername: NCI NIH HHS grantid: R01 CA138738
GroupedDBID	0R~ 0SF 4.4 457 53G 5VS 6I. AACTN AAEDT AAEDW AAFTH AAIKJ AAKRW AALRI AAUCE AAXJY AAXUO ABMAC ABMWF ACGFO ACGFS ADBBV ADEZE AENEX AEXQZ AFTJW AGHFR AITUG ALKID ALMA_UNASSIGNED_HOLDINGS AMRAJ BAWUL BCNDV DIK EBS EJD FCP FDB FRP GROUPED_DOAJ GX1 IXB KQ8 M41 M48 NCXOZ O-L O9- OK1 RCE RIG ROL SSZ AAMRU AAYWO AAYXX ACVFH ADCNI ADVLN AEUPX AFPUW AIGII AKBMS AKRWK AKYEP APXCP CITATION HZ~ IPNFZ CGR CUY CVF ECM EIF NPM 7X8 5PM
ID	FETCH-LOGICAL-c463t-6a8abcdc8519e1c9f918b6d476e9cad15f912e6a2af5a8f9eb105f90760fee6e3
ISICitedReferencesCount	276
ISICitedReferencesURI	http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000432455600020&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN	2211-1247
IngestDate	Tue Sep 30 16:45:39 EDT 2025 Sun Nov 09 11:20:50 EST 2025 Thu Apr 03 07:06:13 EDT 2025 Tue Nov 18 22:07:45 EST 2025 Wed Nov 05 20:54:51 EST 2025 Wed May 17 02:14:14 EDT 2023
IsDoiOpenAccess	true
IsOpenAccess	true
IsPeerReviewed	true
IsScholarly	true
Issue	7
Keywords	armored CAR B-ALL MUC16 interleukin-18 ovarian cancer IL-18 chimeric antigen receptor adoptive transfer CAR T cell
Language	English
License	This is an open access article under the CC BY-NC-ND license. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
LinkModel	OpenURL
MergedId	FETCHMERGED-LOGICAL-c463t-6a8abcdc8519e1c9f918b6d476e9cad15f912e6a2af5a8f9eb105f90760fee6e3
Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Lead Contact These authors contributed equally
OpenAccessLink	http://dx.doi.org/10.1016/j.celrep.2018.04.051
PMID	29768210
PQID	2040755569
PQPubID	23479
PageCount	12
ParticipantIDs	pubmedcentral_primary_oai_pubmedcentral_nih_gov_5986286 proquest_miscellaneous_2040755569 pubmed_primary_29768210 crossref_citationtrail_10_1016_j_celrep_2018_04_051 crossref_primary_10_1016_j_celrep_2018_04_051 elsevier_sciencedirect_doi_10_1016_j_celrep_2018_04_051
PublicationCentury	2000
PublicationDate	2018-05-15
PublicationDateYYYYMMDD	2018-05-15
PublicationDate_xml	– month: 05 year: 2018 text: 2018-05-15 day: 15
PublicationDecade	2010
PublicationPlace	United States
PublicationPlace_xml	– name: United States
PublicationTitle	Cell reports (Cambridge)
PublicationTitleAlternate	Cell Rep
PublicationYear	2018
Publisher	Elsevier Inc
Publisher_xml	– name: Elsevier Inc
References	Brentjens, Latouche, Santos, Marti, Gong, Lyddane, King, Larson, Weiss, Rivière, Sadelain (bib1) 2003; 9 Khan, Kolomeyevskaya, Singel, Grimm, Moysich, Daudi, Grzankowski, Lele, Ylagan, Webster (bib19) 2015; 6 Lee, Kochenderfer, Stetler-Stevenson, Cui, Delbrook, Feldman, Fry, Orentas, Sabatino, Shah (bib22) 2015; 385 Hart, Byrne, Molloy, Usherwood, Berwin (bib14) 2011; 2 Hu, Ren, Luo, Keith, Young, Scholler, Zhao, June (bib15) 2017; 20 Koneru, Purdon, Spriggs, Koneru, Brentjens (bib20) 2015; 4 Mantovani, Sozzani, Locati, Allavena, Sica (bib24) 2002; 23 Yuan, Hsiao, Chen, Chen, Ho, Chen, Liu, Hong, Yu, Chen, Yang (bib33) 2015; 5 Gardner, Wu, Cherian, Fang, Hanafi, Finney, Smithers, Jensen, Riddell, Maloney, Turtle (bib11) 2016; 127 Pegram, Lee, Hayman, Imperato, Tedder, Sadelain, Brentjens (bib27) 2012; 119 Gardner, Finney, Annesley, Brakke, Summers, Leger, Bleakley, Brown, Mgebroff, Kelly-Spratt (bib12) 2017; 129 Chmielewski, Abken (bib7) 2017; 21 Chekmasova, Rao, Nikhamin, Park, Levine, Spriggs, Brentjens (bib5) 2010; 16 Wang, Wang, Lv, Han, Fan, Guo, Wang, Han (bib32) 2015; 23 Brown, Alizadeh, Starr, Weng, Wagner, Naranjo, Ostberg, Blanchard, Kilpatrick, Simpson (bib4) 2016; 375 Kalos, Levine, Porter, Katz, Grupp, Bagg, June (bib18) 2011; 3 Davila, Riviere, Wang, Bartido, Park, Curran, Chung, Stefanski, Borquez-Ojeda, Olszewska (bib8) 2014; 6 Louis, Savoldo, Dotti, Pule, Yvon, Myers, Rossig, Russell, Diouf, Liu (bib23) 2011; 118 Maude, Frey, Shaw, Aplenc, Barrett, Bunin, Chew, Gonzalez, Zheng, Lacey (bib25) 2014; 371 Zunder, Finck, Behbehani, Amir, Krishnaswamy, Gonzalez, Lorang, Bjornson, Spitzer, Bodenmiller (bib34) 2015; 10 Gong, Latouche, Krause, Heston, Bander, Sadelain (bib13) 1999; 1 Feng, Guo, Liu, Dai, Wang, Lv, Huang, Yang, Han (bib9) 2017; 10 Jackson, Rafiq, Brentjens (bib16) 2016; 13 Brentjens, Santos, Nikhamin, Yeh, Matsushita, La Perle, Quintás-Cardama, Larson, Sadelain (bib2) 2007; 13 Gajewski, Meng, Blank, Brown, Kacha, Kline, Harlin (bib10) 2006; 213 O’Rourke, Nasrallah, Desai, Melenhorst, Mansfield, Morrissette, Martinez-Lage, Brem, Maloney, Shen (bib26) 2017; 9 Richards, Chang, Blaser, Caligiuri, Zheng, Liu (bib29) 2006; 108 Cherkassky, Morello, Villena-Vargas, Feng, Dimitrov, Jones, Sadelain, Adusumilli (bib6) 2016; 126 John, Devaud, Duong, Yong, Beavis, Haynes, Chow, Smyth, Kershaw, Darcy (bib17) 2013; 19 Pegram, Purdon, van Leeuwen, Curran, Giralt, Barker, Brentjens (bib28) 2015; 29 Krevvata, Silva, Manavalan, Galan-Diez, Kode, Matthews, Park, Zhang, Galili, Nickolas (bib21) 2014; 124 Brentjens, Davila, Riviere, Park, Wang, Cowell, Bartido, Stefanski, Taylor, Olszewska (bib3) 2013; 5 Spitzer, Gherardini, Fragiadakis, Bhattacharya, Yuan, Hotson, Finck, Carmi, Zunder, Fantl (bib31) 2015; 349 Sotillo, Barrett, Black, Bagashev, Oldridge, Wu, Sussman, Lanauze, Ruella, Gazzara (bib30) 2015; 5 Sotillo (10.1016/j.celrep.2018.04.051_bib30) 2015; 5 Gardner (10.1016/j.celrep.2018.04.051_bib11) 2016; 127 Davila (10.1016/j.celrep.2018.04.051_bib8) 2014; 6 Maude (10.1016/j.celrep.2018.04.051_bib25) 2014; 371 Pegram (10.1016/j.celrep.2018.04.051_bib27) 2012; 119 Richards (10.1016/j.celrep.2018.04.051_bib29) 2006; 108 Spitzer (10.1016/j.celrep.2018.04.051_bib31) 2015; 349 O’Rourke (10.1016/j.celrep.2018.04.051_bib26) 2017; 9 Wang (10.1016/j.celrep.2018.04.051_bib32) 2015; 23 Chmielewski (10.1016/j.celrep.2018.04.051_bib7) 2017; 21 Brentjens (10.1016/j.celrep.2018.04.051_bib2) 2007; 13 Zunder (10.1016/j.celrep.2018.04.051_bib34) 2015; 10 Kalos (10.1016/j.celrep.2018.04.051_bib18) 2011; 3 Pegram (10.1016/j.celrep.2018.04.051_bib28) 2015; 29 Krevvata (10.1016/j.celrep.2018.04.051_bib21) 2014; 124 Brentjens (10.1016/j.celrep.2018.04.051_bib3) 2013; 5 Hart (10.1016/j.celrep.2018.04.051_bib14) 2011; 2 Gong (10.1016/j.celrep.2018.04.051_bib13) 1999; 1 Hu (10.1016/j.celrep.2018.04.051_bib15) 2017; 20 Gardner (10.1016/j.celrep.2018.04.051_bib12) 2017; 129 Jackson (10.1016/j.celrep.2018.04.051_bib16) 2016; 13 Chekmasova (10.1016/j.celrep.2018.04.051_bib5) 2010; 16 Gajewski (10.1016/j.celrep.2018.04.051_bib10) 2006; 213 Lee (10.1016/j.celrep.2018.04.051_bib22) 2015; 385 Cherkassky (10.1016/j.celrep.2018.04.051_bib6) 2016; 126 Feng (10.1016/j.celrep.2018.04.051_bib9) 2017; 10 Yuan (10.1016/j.celrep.2018.04.051_bib33) 2015; 5 Brown (10.1016/j.celrep.2018.04.051_bib4) 2016; 375 Khan (10.1016/j.celrep.2018.04.051_bib19) 2015; 6 Louis (10.1016/j.celrep.2018.04.051_bib23) 2011; 118 John (10.1016/j.celrep.2018.04.051_bib17) 2013; 19 Mantovani (10.1016/j.celrep.2018.04.051_bib24) 2002; 23 Brentjens (10.1016/j.celrep.2018.04.051_bib1) 2003; 9 Koneru (10.1016/j.celrep.2018.04.051_bib20) 2015; 4
References_xml	– volume: 119 start-page: 4133 year: 2012 end-page: 4141 ident: bib27 article-title: Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning publication-title: Blood – volume: 6 start-page: 11310 year: 2015 end-page: 11326 ident: bib19 article-title: Targeting myeloid cells in the tumor microenvironment enhances vaccine efficacy in murine epithelial ovarian cancer publication-title: Oncotarget – volume: 108 start-page: 246 year: 2006 end-page: 252 ident: bib29 article-title: Tumor growth impedes natural-killer-cell maturation in the bone marrow publication-title: Blood – volume: 13 start-page: 370 year: 2016 end-page: 383 ident: bib16 article-title: Driving CAR T-cells forward publication-title: Nat. Rev. Clin. Oncol. – volume: 5 start-page: 14273 year: 2015 ident: bib33 article-title: Opposite effects of M1 and M2 macrophage subtypes on lung cancer progression publication-title: Sci. Rep. – volume: 4 start-page: e994446 year: 2015 ident: bib20 article-title: IL-12 secreting tumor-targeted chimeric antigen receptor T cells eradicate ovarian tumors publication-title: OncoImmunology – volume: 349 start-page: 1259425 year: 2015 ident: bib31 article-title: IMMUNOLOGY. An interactive reference framework for modeling a dynamic immune system publication-title: Science – volume: 126 start-page: 3130 year: 2016 end-page: 3144 ident: bib6 article-title: Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition publication-title: J. Clin. Invest. – volume: 1 start-page: 123 year: 1999 end-page: 127 ident: bib13 article-title: Cancer patient T cells genetically targeted to prostate-specific membrane antigen specifically lyse prostate cancer cells and release cytokines in response to prostate-specific membrane antigen publication-title: Neoplasia – volume: 20 start-page: 3025 year: 2017 end-page: 3033 ident: bib15 article-title: Augmentation of antitumor immunity by human and mouse CAR T cells secreting IL-18 publication-title: Cell Rep. – volume: 29 start-page: 415 year: 2015 end-page: 422 ident: bib28 article-title: IL-12-secreting CD19-targeted cord blood-derived T cells for the immunotherapy of B-cell acute lymphoblastic leukemia publication-title: Leukemia – volume: 23 start-page: 549 year: 2002 end-page: 555 ident: bib24 article-title: Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes publication-title: Trends Immunol. – volume: 10 start-page: 316 year: 2015 end-page: 333 ident: bib34 article-title: Palladium-based mass tag cell barcoding with a doublet-filtering scheme and single-cell deconvolution algorithm publication-title: Nat. Protoc. – volume: 13 start-page: 5426 year: 2007 end-page: 5435 ident: bib2 article-title: Genetically targeted T cells eradicate systemic acute lymphoblastic leukemia xenografts publication-title: Clin. Cancer Res. – volume: 124 start-page: 2834 year: 2014 end-page: 2846 ident: bib21 article-title: Inhibition of leukemia cell engraftment and disease progression in mice by osteoblasts publication-title: Blood – volume: 375 start-page: 2561 year: 2016 end-page: 2569 ident: bib4 article-title: Regression of glioblastoma after chimeric antigen receptor T-cell therapy publication-title: N. Engl. J. Med. – volume: 3 start-page: 95ra73 year: 2011 ident: bib18 article-title: T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia publication-title: Sci. Transl. Med. – volume: 6 start-page: 224ra25 year: 2014 ident: bib8 article-title: Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia publication-title: Sci. Transl. Med. – volume: 118 start-page: 6050 year: 2011 end-page: 6056 ident: bib23 article-title: Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma publication-title: Blood – volume: 9 start-page: 279 year: 2003 end-page: 286 ident: bib1 article-title: Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15 publication-title: Nat. Med. – volume: 5 start-page: 177ra38 year: 2013 ident: bib3 article-title: CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia publication-title: Sci. Transl. Med. – volume: 9 start-page: eaaa0984 year: 2017 ident: bib26 article-title: A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma publication-title: Sci. Transl. Med. – volume: 5 start-page: 1282 year: 2015 end-page: 1295 ident: bib30 article-title: Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy publication-title: Cancer Discov. – volume: 371 start-page: 1507 year: 2014 end-page: 1517 ident: bib25 article-title: Chimeric antigen receptor T cells for sustained remissions in leukemia publication-title: N. Engl. J. Med. – volume: 213 start-page: 131 year: 2006 end-page: 145 ident: bib10 article-title: Immune resistance orchestrated by the tumor microenvironment publication-title: Immunol. Rev. – volume: 16 start-page: 3594 year: 2010 end-page: 3606 ident: bib5 article-title: Successful eradication of established peritoneal ovarian tumors in SCID-Beige mice following adoptive transfer of T cells genetically targeted to the MUC16 antigen publication-title: Clin. Cancer Res. – volume: 385 start-page: 517 year: 2015 end-page: 528 ident: bib22 article-title: T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial publication-title: Lancet – volume: 127 start-page: 2406 year: 2016 end-page: 2410 ident: bib11 article-title: Acquisition of a CD19-negative myeloid phenotype allows immune escape of MLL-rearranged B-ALL from CD19 CAR-T-cell therapy publication-title: Blood – volume: 2 start-page: 29 year: 2011 ident: bib14 article-title: IL-10 immunomodulation of myeloid cells regulates a murine model of ovarian cancer publication-title: Front. Immunol. – volume: 19 start-page: 5636 year: 2013 end-page: 5646 ident: bib17 article-title: Anti-PD-1 antibody therapy potently enhances the eradication of established tumors by gene-modified T cells publication-title: Clin. Cancer Res. – volume: 10 start-page: 4 year: 2017 ident: bib9 article-title: Cocktail treatment with EGFR-specific and CD133-specific chimeric antigen receptor-modified T cells in a patient with advanced cholangiocarcinoma publication-title: J. Hematol. Oncol. – volume: 21 start-page: 3205 year: 2017 end-page: 3219 ident: bib7 article-title: CAR T cells releasing IL-18 convert to T-Bet publication-title: Cell Rep. – volume: 23 start-page: 184 year: 2015 end-page: 191 ident: bib32 article-title: Treatment of CD33-directed chimeric antigen receptor-modified T cells in one patient with relapsed and refractory acute myeloid leukemia publication-title: Mol. Ther. – volume: 129 start-page: 3322 year: 2017 end-page: 3331 ident: bib12 article-title: Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults publication-title: Blood – volume: 118 start-page: 6050 year: 2011 ident: 10.1016/j.celrep.2018.04.051_bib23 article-title: Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma publication-title: Blood doi: 10.1182/blood-2011-05-354449 – volume: 13 start-page: 370 year: 2016 ident: 10.1016/j.celrep.2018.04.051_bib16 article-title: Driving CAR T-cells forward publication-title: Nat. Rev. Clin. Oncol. doi: 10.1038/nrclinonc.2016.36 – volume: 19 start-page: 5636 year: 2013 ident: 10.1016/j.celrep.2018.04.051_bib17 article-title: Anti-PD-1 antibody therapy potently enhances the eradication of established tumors by gene-modified T cells publication-title: Clin. Cancer Res. doi: 10.1158/1078-0432.CCR-13-0458 – volume: 129 start-page: 3322 year: 2017 ident: 10.1016/j.celrep.2018.04.051_bib12 article-title: Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults publication-title: Blood doi: 10.1182/blood-2017-02-769208 – volume: 23 start-page: 184 year: 2015 ident: 10.1016/j.celrep.2018.04.051_bib32 article-title: Treatment of CD33-directed chimeric antigen receptor-modified T cells in one patient with relapsed and refractory acute myeloid leukemia publication-title: Mol. Ther. doi: 10.1038/mt.2014.164 – volume: 10 start-page: 4 year: 2017 ident: 10.1016/j.celrep.2018.04.051_bib9 article-title: Cocktail treatment with EGFR-specific and CD133-specific chimeric antigen receptor-modified T cells in a patient with advanced cholangiocarcinoma publication-title: J. Hematol. Oncol. doi: 10.1186/s13045-016-0378-7 – volume: 4 start-page: e994446 year: 2015 ident: 10.1016/j.celrep.2018.04.051_bib20 article-title: IL-12 secreting tumor-targeted chimeric antigen receptor T cells eradicate ovarian tumors in vivo publication-title: OncoImmunology doi: 10.4161/2162402X.2014.994446 – volume: 1 start-page: 123 year: 1999 ident: 10.1016/j.celrep.2018.04.051_bib13 article-title: Cancer patient T cells genetically targeted to prostate-specific membrane antigen specifically lyse prostate cancer cells and release cytokines in response to prostate-specific membrane antigen publication-title: Neoplasia doi: 10.1038/sj.neo.7900018 – volume: 349 start-page: 1259425 year: 2015 ident: 10.1016/j.celrep.2018.04.051_bib31 article-title: IMMUNOLOGY. An interactive reference framework for modeling a dynamic immune system publication-title: Science doi: 10.1126/science.1259425 – volume: 6 start-page: 224ra25 year: 2014 ident: 10.1016/j.celrep.2018.04.051_bib8 article-title: Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia publication-title: Sci. Transl. Med. doi: 10.1126/scitranslmed.3008226 – volume: 21 start-page: 3205 year: 2017 ident: 10.1016/j.celrep.2018.04.051_bib7 article-title: CAR T cells releasing IL-18 convert to T-Bethigh FoxO1low effectors that exhibit augmented activity against advanced solid tumors publication-title: Cell Rep. doi: 10.1016/j.celrep.2017.11.063 – volume: 20 start-page: 3025 year: 2017 ident: 10.1016/j.celrep.2018.04.051_bib15 article-title: Augmentation of antitumor immunity by human and mouse CAR T cells secreting IL-18 publication-title: Cell Rep. doi: 10.1016/j.celrep.2017.09.002 – volume: 13 start-page: 5426 year: 2007 ident: 10.1016/j.celrep.2018.04.051_bib2 article-title: Genetically targeted T cells eradicate systemic acute lymphoblastic leukemia xenografts publication-title: Clin. Cancer Res. doi: 10.1158/1078-0432.CCR-07-0674 – volume: 119 start-page: 4133 year: 2012 ident: 10.1016/j.celrep.2018.04.051_bib27 article-title: Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning publication-title: Blood doi: 10.1182/blood-2011-12-400044 – volume: 108 start-page: 246 year: 2006 ident: 10.1016/j.celrep.2018.04.051_bib29 article-title: Tumor growth impedes natural-killer-cell maturation in the bone marrow publication-title: Blood doi: 10.1182/blood-2005-11-4535 – volume: 371 start-page: 1507 year: 2014 ident: 10.1016/j.celrep.2018.04.051_bib25 article-title: Chimeric antigen receptor T cells for sustained remissions in leukemia publication-title: N. Engl. J. Med. doi: 10.1056/NEJMoa1407222 – volume: 16 start-page: 3594 year: 2010 ident: 10.1016/j.celrep.2018.04.051_bib5 article-title: Successful eradication of established peritoneal ovarian tumors in SCID-Beige mice following adoptive transfer of T cells genetically targeted to the MUC16 antigen publication-title: Clin. Cancer Res. doi: 10.1158/1078-0432.CCR-10-0192 – volume: 2 start-page: 29 year: 2011 ident: 10.1016/j.celrep.2018.04.051_bib14 article-title: IL-10 immunomodulation of myeloid cells regulates a murine model of ovarian cancer publication-title: Front. Immunol. doi: 10.3389/fimmu.2011.00029 – volume: 29 start-page: 415 year: 2015 ident: 10.1016/j.celrep.2018.04.051_bib28 article-title: IL-12-secreting CD19-targeted cord blood-derived T cells for the immunotherapy of B-cell acute lymphoblastic leukemia publication-title: Leukemia doi: 10.1038/leu.2014.215 – volume: 5 start-page: 14273 year: 2015 ident: 10.1016/j.celrep.2018.04.051_bib33 article-title: Opposite effects of M1 and M2 macrophage subtypes on lung cancer progression publication-title: Sci. Rep. doi: 10.1038/srep14273 – volume: 124 start-page: 2834 year: 2014 ident: 10.1016/j.celrep.2018.04.051_bib21 article-title: Inhibition of leukemia cell engraftment and disease progression in mice by osteoblasts publication-title: Blood doi: 10.1182/blood-2013-07-517219 – volume: 385 start-page: 517 year: 2015 ident: 10.1016/j.celrep.2018.04.051_bib22 article-title: T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial publication-title: Lancet doi: 10.1016/S0140-6736(14)61403-3 – volume: 6 start-page: 11310 year: 2015 ident: 10.1016/j.celrep.2018.04.051_bib19 article-title: Targeting myeloid cells in the tumor microenvironment enhances vaccine efficacy in murine epithelial ovarian cancer publication-title: Oncotarget doi: 10.18632/oncotarget.3597 – volume: 5 start-page: 1282 year: 2015 ident: 10.1016/j.celrep.2018.04.051_bib30 article-title: Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy publication-title: Cancer Discov. doi: 10.1158/2159-8290.CD-15-1020 – volume: 10 start-page: 316 year: 2015 ident: 10.1016/j.celrep.2018.04.051_bib34 article-title: Palladium-based mass tag cell barcoding with a doublet-filtering scheme and single-cell deconvolution algorithm publication-title: Nat. Protoc. doi: 10.1038/nprot.2015.020 – volume: 213 start-page: 131 year: 2006 ident: 10.1016/j.celrep.2018.04.051_bib10 article-title: Immune resistance orchestrated by the tumor microenvironment publication-title: Immunol. Rev. doi: 10.1111/j.1600-065X.2006.00442.x – volume: 126 start-page: 3130 year: 2016 ident: 10.1016/j.celrep.2018.04.051_bib6 article-title: Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition publication-title: J. Clin. Invest. doi: 10.1172/JCI83092 – volume: 23 start-page: 549 year: 2002 ident: 10.1016/j.celrep.2018.04.051_bib24 article-title: Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes publication-title: Trends Immunol. doi: 10.1016/S1471-4906(02)02302-5 – volume: 375 start-page: 2561 year: 2016 ident: 10.1016/j.celrep.2018.04.051_bib4 article-title: Regression of glioblastoma after chimeric antigen receptor T-cell therapy publication-title: N. Engl. J. Med. doi: 10.1056/NEJMoa1610497 – volume: 9 start-page: eaaa0984 year: 2017 ident: 10.1016/j.celrep.2018.04.051_bib26 article-title: A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma publication-title: Sci. Transl. Med. doi: 10.1126/scitranslmed.aaa0984 – volume: 127 start-page: 2406 year: 2016 ident: 10.1016/j.celrep.2018.04.051_bib11 article-title: Acquisition of a CD19-negative myeloid phenotype allows immune escape of MLL-rearranged B-ALL from CD19 CAR-T-cell therapy publication-title: Blood doi: 10.1182/blood-2015-08-665547 – volume: 3 start-page: 95ra73 year: 2011 ident: 10.1016/j.celrep.2018.04.051_bib18 article-title: T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia publication-title: Sci. Transl. Med. doi: 10.1126/scitranslmed.3002842 – volume: 5 start-page: 177ra38 year: 2013 ident: 10.1016/j.celrep.2018.04.051_bib3 article-title: CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia publication-title: Sci. Transl. Med. doi: 10.1126/scitranslmed.3005930 – volume: 9 start-page: 279 year: 2003 ident: 10.1016/j.celrep.2018.04.051_bib1 article-title: Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15 publication-title: Nat. Med. doi: 10.1038/nm827
SSID	ssj0000601194
Score	2.6192603
Snippet	Chimeric antigen receptor (CAR) T cell therapy has proven clinically beneficial against B cell acute lymphoblastic leukemia and non-Hodgkin’s lymphoma.... Chimeric antigen receptor (CAR) T cell therapy has proven clinically beneficial against B cell acute lymphoblastic leukemia and non-Hodgkin's lymphoma.... Chimeric antigen receptor (CAR) T cell therapy has proven clinically beneficial against B cell acute lymphoblastic leukemia and non-Hodgkin's lymphoma.... Chimeric antigen receptor (CAR) T cell therapy has proven clinically beneficial against B cell acute lymphoblastic leukemia and non-Hodgkin’s lymphoma....
SourceID	pubmedcentral proquest pubmed crossref elsevier
SourceType	Open Access Repository Aggregation Database Index Database Enrichment Source Publisher
StartPage	2130
SubjectTerms	adoptive transfer Animals Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use armored CAR Autocrine Communication - drug effects B-ALL B-Lymphocytes - drug effects CAR T cell Cell Proliferation - drug effects Cell Survival - drug effects chimeric antigen receptor Disease Models, Animal Humans IL-18 Immune System - drug effects Immune System - metabolism Immunotherapy Immunotherapy, Adoptive interleukin-18 Interleukin-18 - metabolism Mice, Inbred C57BL Mice, SCID MUC16 Neoplasms - drug therapy Neoplasms - immunology Neoplasms - pathology ovarian cancer Signal Transduction - drug effects T-Lymphocytes - drug effects T-Lymphocytes - immunology Tumor Microenvironment - drug effects Xenograft Model Antitumor Assays
Title	Engineered Tumor-Targeted T Cells Mediate Enhanced Anti-Tumor Efficacy Both Directly and through Activation of the Endogenous Immune System
URI	https://dx.doi.org/10.1016/j.celrep.2018.04.051 https://www.ncbi.nlm.nih.gov/pubmed/29768210 https://www.proquest.com/docview/2040755569 https://pubmed.ncbi.nlm.nih.gov/PMC5986286
Volume	23
WOSCitedRecordID	wos000432455600020&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText	1
inHoldings	1
isFullTextHit
isPrint
journalDatabaseRights	– providerCode: PRVAON databaseName: DOAJ Directory of Open Access Journals customDbUrl: eissn: 2211-1247 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0000601194 issn: 2211-1247 databaseCode: DOA dateStart: 20120101 isFulltext: true titleUrlDefault: https://www.doaj.org/ providerName: Directory of Open Access Journals
link	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1Lj9MwELbKAhIXxJvyWBmJW5UqdV72sayKQELLHoroLXITR00JSdU2y5a_wC_lXzAT22m7BZY9cIka13ESzxd77Jn5hpDXkmeRnHrCYYGXOn6UTh3OReYgmd0UZhjflQ2J64fo9JRPJuKs0_lpY2HOi6gs-cWFWPxXUUMZCBtDZ68h7rZRKIDfIHQ4gtjh-E-CtwyDoEmO66_V0hk3zt542jtRRbFqjDOgYvZG5Uzb_4flOneayphpGcSWbHpvQIRmQCw2xs9Sp_QZJjYlmnUwGJVpZche32O8iTJE6LuaL966tVCg6dgGi-3uRYBa_z3XIUT1suqd9bdbul9qLP9YyFQuqtaNqKk8gel3VreFn_O5-iaho1b1Mt9oexbm_spte2aTY8DRPq_DPPVYyBh63jFNztlXvykzg7kOXjagjfZGZmP_UeZU820dzCB6M2PeT1QBfYK-f7zhwjW0uHuE3Zcm0ta90XrOzWPdSoytxK4fuxjsf5NFgRA7q3-tNCD5HvpAtK9lAz0bb8TDx_mTInW4ULrs77ujQI3vkbtm5UOHGrH3SUeVD8htnQt185D82OKW7uOWjmmDW2pwSy1u6Ra31OKWIm6pxS0F3FKDW7rFLa0yKMWGLG6pxi3VuH1EPr0djU_eOSZTiJP4obd2QsnlNEkTWD4INUhEJgZ8GqZ-FCqRyHQQQAFToWQyC2B0EqCguFCGVulMqVB5j8lRWZXqKaG-Cr1UZqDXRcoXmSvYIGMiCD2ZBkGSqi7xbLfHiaHRx2wuRfw3qXeJ01610DQyV9SPrERjowprFTcGnF5x5SsLgBhmCjT_yVJBR0IlH9YHQRCKLnmiAdE-C4NVCWcDF-67B5W2ArLQ7_9T5rOGjR4TPDAePrvmGz4nd7Yf-gtytF7W6iW5lZyv89XymNyIJvy4-UR-ATOSA4k
linkProvider	Directory of Open Access Journals
openUrl	ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Engineered+Tumor-Targeted+T+Cells+Mediate+Enhanced+Anti-Tumor+Efficacy+Both+Directly+and+through+Activation+of+the+Endogenous+Immune+System&rft.jtitle=Cell+reports+%28Cambridge%29&rft.au=Avanzi%2C+Mauro+P.&rft.au=Yeku%2C+Oladapo&rft.au=Li%2C+Xinghuo&rft.au=Wijewarnasuriya%2C+Dinali+P.&rft.date=2018-05-15&rft.issn=2211-1247&rft.eissn=2211-1247&rft.volume=23&rft.issue=7&rft.spage=2130&rft.epage=2141&rft_id=info:doi/10.1016%2Fj.celrep.2018.04.051&rft.externalDBID=n%2Fa&rft.externalDocID=10_1016_j_celrep_2018_04_051
thumbnail_l	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2211-1247&client=summon
thumbnail_m	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2211-1247&client=summon
thumbnail_s	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2211-1247&client=summon