Engineering adoptive T cell therapy to co-opt Fas ligand-mediated death signaling in ovarian cancer enhances therapeutic efficacy
BackgroundIn the USA, more than 50% of patients with ovarian cancer die within 5 years of diagnosis, highlighting the need for therapeutic innovations. Mesothelin (MSLN) is a candidate immunotherapy target; it is overexpressed by ovarian tumors and contributes to malignant/invasive phenotypes, makin...
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| Vydané v: | Journal for immunotherapy of cancer Ročník 10; číslo 3; s. e003959 |
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| Hlavní autori: | , , , , , , |
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| Jazyk: | English |
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England
BMJ Publishing Group Ltd
01.03.2022
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| Abstract | BackgroundIn the USA, more than 50% of patients with ovarian cancer die within 5 years of diagnosis, highlighting the need for therapeutic innovations. Mesothelin (MSLN) is a candidate immunotherapy target; it is overexpressed by ovarian tumors and contributes to malignant/invasive phenotypes, making tumor antigen loss disadvantageous. We previously showed that MSLN-specific T cell receptor (TCR)-engineered T cells preferentially accumulate within established tumors, delay tumor growth, and significantly prolong survival in the ID8VEGF mouse model that replicates many aspects of human disease. However, T cell persistence and antitumor activity were not sustained. We therefore focused on Fas/FasL signaling that can induce activation-induced cell death, an apoptotic mechanism that regulates T cell expansion. Upregulation of FasL by tumor cells and tumor vasculature has been detected in the tumor microenvironment (TME) of human and murine ovarian cancers, can induce apoptosis in infiltrating, Fas (CD95) receptor-expressing lymphocytes, and can protect ovarian cancers from tumor-infiltrating lymphocytes.MethodsTo overcome potential FasL-mediated immune evasion and enhance T cell responses, we generated an immunomodulatory fusion protein (IFP) containing the Fas extracellular binding domain fused to a 4-1BB co-stimulatory domain, rather than the natural death domain. Murine T cells were engineered to express an MSLN-specific TCR (TCR1045), alone or with the IFP, transferred into ID8VEGF tumor-bearing mice and evaluated for persistence, proliferation, cytokine production and efficacy. Human T cells were similarly engineered to express an MSLN-specific TCR (TCR530) alone or with a truncated Fas receptor or a Fas-4-1BB IFP and evaluated for cytokine production and tumor lysis.ResultsRelative to murine T cells expressing only TCR1045, T cells expressing both TCR1045 and a Fas-4-1BB IFP preferentially persisted in the TME of tumor-bearing mice, with improved T cell proliferation and survival. Moreover, TCR1045/IFP+ T cells significantly prolonged survival in tumor-bearing mice, compared with TCR1045-only T cells. Human T cells expressing TCR530 and a Fas-4-1BB IFP exhibit enhanced functional activity and viability compared with cells with only TCR530.ConclusionsAs many ovarian tumors overexpress FasL, an IFP that converts the Fas-mediated death signal into pro-survival and proliferative signals may be used to enhance engineered adoptive T cell therapy for patients. |
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| AbstractList | Background In the USA, more than 50% of patients with ovarian cancer die within 5 years of diagnosis, highlighting the need for therapeutic innovations. Mesothelin (MSLN) is a candidate immunotherapy target; it is overexpressed by ovarian tumors and contributes to malignant/invasive phenotypes, making tumor antigen loss disadvantageous. We previously showed that MSLN-specific T cell receptor (TCR)-engineered T cells preferentially accumulate within established tumors, delay tumor growth, and significantly prolong survival in the ID8VEGF mouse model that replicates many aspects of human disease. However, T cell persistence and antitumor activity were not sustained. We therefore focused on Fas/FasL signaling that can induce activation-induced cell death, an apoptotic mechanism that regulates T cell expansion. Upregulation of FasL by tumor cells and tumor vasculature has been detected in the tumor microenvironment (TME) of human and murine ovarian cancers, can induce apoptosis in infiltrating, Fas (CD95) receptor-expressing lymphocytes, and can protect ovarian cancers from tumor-infiltrating lymphocytes.Methods To overcome potential FasL-mediated immune evasion and enhance T cell responses, we generated an immunomodulatory fusion protein (IFP) containing the Fas extracellular binding domain fused to a 4-1BB co-stimulatory domain, rather than the natural death domain. Murine T cells were engineered to express an MSLN-specific TCR (TCR1045), alone or with the IFP, transferred into ID8VEGF tumor-bearing mice and evaluated for persistence, proliferation, cytokine production and efficacy. Human T cells were similarly engineered to express an MSLN-specific TCR (TCR530) alone or with a truncated Fas receptor or a Fas-4-1BB IFP and evaluated for cytokine production and tumor lysis.Results Relative to murine T cells expressing only TCR1045, T cells expressing both TCR1045 and a Fas-4-1BB IFP preferentially persisted in the TME of tumor-bearing mice, with improved T cell proliferation and survival. Moreover, TCR1045/IFP+ T cells significantly prolonged survival in tumor-bearing mice, compared with TCR1045-only T cells. Human T cells expressing TCR530 and a Fas-4-1BB IFP exhibit enhanced functional activity and viability compared with cells with only TCR530.Conclusions As many ovarian tumors overexpress FasL, an IFP that converts the Fas-mediated death signal into pro-survival and proliferative signals may be used to enhance engineered adoptive T cell therapy for patients. In the USA, more than 50% of patients with ovarian cancer die within 5 years of diagnosis, highlighting the need for therapeutic innovations. Mesothelin (MSLN) is a candidate immunotherapy target; it is overexpressed by ovarian tumors and contributes to malignant/invasive phenotypes, making tumor antigen loss disadvantageous. We previously showed that MSLN-specific T cell receptor (TCR)-engineered T cells preferentially accumulate within established tumors, delay tumor growth, and significantly prolong survival in the ID8VEGF mouse model that replicates many aspects of human disease. However, T cell persistence and antitumor activity were not sustained. We therefore focused on Fas/FasL signaling that can induce activation-induced cell death, an apoptotic mechanism that regulates T cell expansion. Upregulation of FasL by tumor cells and tumor vasculature has been detected in the tumor microenvironment (TME) of human and murine ovarian cancers, can induce apoptosis in infiltrating, Fas (CD95) receptor-expressing lymphocytes, and can protect ovarian cancers from tumor-infiltrating lymphocytes.BACKGROUNDIn the USA, more than 50% of patients with ovarian cancer die within 5 years of diagnosis, highlighting the need for therapeutic innovations. Mesothelin (MSLN) is a candidate immunotherapy target; it is overexpressed by ovarian tumors and contributes to malignant/invasive phenotypes, making tumor antigen loss disadvantageous. We previously showed that MSLN-specific T cell receptor (TCR)-engineered T cells preferentially accumulate within established tumors, delay tumor growth, and significantly prolong survival in the ID8VEGF mouse model that replicates many aspects of human disease. However, T cell persistence and antitumor activity were not sustained. We therefore focused on Fas/FasL signaling that can induce activation-induced cell death, an apoptotic mechanism that regulates T cell expansion. Upregulation of FasL by tumor cells and tumor vasculature has been detected in the tumor microenvironment (TME) of human and murine ovarian cancers, can induce apoptosis in infiltrating, Fas (CD95) receptor-expressing lymphocytes, and can protect ovarian cancers from tumor-infiltrating lymphocytes.To overcome potential FasL-mediated immune evasion and enhance T cell responses, we generated an immunomodulatory fusion protein (IFP) containing the Fas extracellular binding domain fused to a 4-1BB co-stimulatory domain, rather than the natural death domain. Murine T cells were engineered to express an MSLN-specific TCR (TCR1045), alone or with the IFP, transferred into ID8VEGF tumor-bearing mice and evaluated for persistence, proliferation, cytokine production and efficacy. Human T cells were similarly engineered to express an MSLN-specific TCR (TCR530) alone or with a truncated Fas receptor or a Fas-4-1BB IFP and evaluated for cytokine production and tumor lysis.METHODSTo overcome potential FasL-mediated immune evasion and enhance T cell responses, we generated an immunomodulatory fusion protein (IFP) containing the Fas extracellular binding domain fused to a 4-1BB co-stimulatory domain, rather than the natural death domain. Murine T cells were engineered to express an MSLN-specific TCR (TCR1045), alone or with the IFP, transferred into ID8VEGF tumor-bearing mice and evaluated for persistence, proliferation, cytokine production and efficacy. Human T cells were similarly engineered to express an MSLN-specific TCR (TCR530) alone or with a truncated Fas receptor or a Fas-4-1BB IFP and evaluated for cytokine production and tumor lysis.Relative to murine T cells expressing only TCR1045, T cells expressing both TCR1045 and a Fas-4-1BB IFP preferentially persisted in the TME of tumor-bearing mice, with improved T cell proliferation and survival. Moreover, TCR1045/IFP+ T cells significantly prolonged survival in tumor-bearing mice, compared with TCR1045-only T cells. Human T cells expressing TCR530 and a Fas-4-1BB IFP exhibit enhanced functional activity and viability compared with cells with only TCR530.RESULTSRelative to murine T cells expressing only TCR1045, T cells expressing both TCR1045 and a Fas-4-1BB IFP preferentially persisted in the TME of tumor-bearing mice, with improved T cell proliferation and survival. Moreover, TCR1045/IFP+ T cells significantly prolonged survival in tumor-bearing mice, compared with TCR1045-only T cells. Human T cells expressing TCR530 and a Fas-4-1BB IFP exhibit enhanced functional activity and viability compared with cells with only TCR530.As many ovarian tumors overexpress FasL, an IFP that converts the Fas-mediated death signal into pro-survival and proliferative signals may be used to enhance engineered adoptive T cell therapy for patients.CONCLUSIONSAs many ovarian tumors overexpress FasL, an IFP that converts the Fas-mediated death signal into pro-survival and proliferative signals may be used to enhance engineered adoptive T cell therapy for patients. BackgroundIn the USA, more than 50% of patients with ovarian cancer die within 5 years of diagnosis, highlighting the need for therapeutic innovations. Mesothelin (MSLN) is a candidate immunotherapy target; it is overexpressed by ovarian tumors and contributes to malignant/invasive phenotypes, making tumor antigen loss disadvantageous. We previously showed that MSLN-specific T cell receptor (TCR)-engineered T cells preferentially accumulate within established tumors, delay tumor growth, and significantly prolong survival in the ID8VEGF mouse model that replicates many aspects of human disease. However, T cell persistence and antitumor activity were not sustained. We therefore focused on Fas/FasL signaling that can induce activation-induced cell death, an apoptotic mechanism that regulates T cell expansion. Upregulation of FasL by tumor cells and tumor vasculature has been detected in the tumor microenvironment (TME) of human and murine ovarian cancers, can induce apoptosis in infiltrating, Fas (CD95) receptor-expressing lymphocytes, and can protect ovarian cancers from tumor-infiltrating lymphocytes.MethodsTo overcome potential FasL-mediated immune evasion and enhance T cell responses, we generated an immunomodulatory fusion protein (IFP) containing the Fas extracellular binding domain fused to a 4-1BB co-stimulatory domain, rather than the natural death domain. Murine T cells were engineered to express an MSLN-specific TCR (TCR1045), alone or with the IFP, transferred into ID8VEGF tumor-bearing mice and evaluated for persistence, proliferation, cytokine production and efficacy. Human T cells were similarly engineered to express an MSLN-specific TCR (TCR530) alone or with a truncated Fas receptor or a Fas-4-1BB IFP and evaluated for cytokine production and tumor lysis.ResultsRelative to murine T cells expressing only TCR1045, T cells expressing both TCR1045 and a Fas-4-1BB IFP preferentially persisted in the TME of tumor-bearing mice, with improved T cell proliferation and survival. Moreover, TCR1045/IFP+ T cells significantly prolonged survival in tumor-bearing mice, compared with TCR1045-only T cells. Human T cells expressing TCR530 and a Fas-4-1BB IFP exhibit enhanced functional activity and viability compared with cells with only TCR530.ConclusionsAs many ovarian tumors overexpress FasL, an IFP that converts the Fas-mediated death signal into pro-survival and proliferative signals may be used to enhance engineered adoptive T cell therapy for patients. In the USA, more than 50% of patients with ovarian cancer die within 5 years of diagnosis, highlighting the need for therapeutic innovations. Mesothelin (MSLN) is a candidate immunotherapy target; it is overexpressed by ovarian tumors and contributes to malignant/invasive phenotypes, making tumor antigen loss disadvantageous. We previously showed that MSLN-specific T cell receptor (TCR)-engineered T cells preferentially accumulate within established tumors, delay tumor growth, and significantly prolong survival in the ID8 mouse model that replicates many aspects of human disease. However, T cell persistence and antitumor activity were not sustained. We therefore focused on Fas/FasL signaling that can induce activation-induced cell death, an apoptotic mechanism that regulates T cell expansion. Upregulation of FasL by tumor cells and tumor vasculature has been detected in the tumor microenvironment (TME) of human and murine ovarian cancers, can induce apoptosis in infiltrating, Fas (CD95) receptor-expressing lymphocytes, and can protect ovarian cancers from tumor-infiltrating lymphocytes. To overcome potential FasL-mediated immune evasion and enhance T cell responses, we generated an immunomodulatory fusion protein (IFP) containing the Fas extracellular binding domain fused to a 4-1BB co-stimulatory domain, rather than the natural death domain. Murine T cells were engineered to express an MSLN-specific TCR (TCR ), alone or with the IFP, transferred into ID8 tumor-bearing mice and evaluated for persistence, proliferation, cytokine production and efficacy. Human T cells were similarly engineered to express an MSLN-specific TCR (TCR ) alone or with a truncated Fas receptor or a Fas-4-1BB IFP and evaluated for cytokine production and tumor lysis. Relative to murine T cells expressing only TCR , T cells expressing TCR and a Fas-4-1BB IFP preferentially persisted in the TME of tumor-bearing mice, with improved T cell proliferation and survival. Moreover, TCR /IFP T cells significantly prolonged survival in tumor-bearing mice, compared with TCR -only T cells. Human T cells expressing TCR and a Fas-4-1BB IFP exhibit enhanced functional activity and viability compared with cells with only TCR . As many ovarian tumors overexpress FasL, an IFP that converts the Fas-mediated death signal into pro-survival and proliferative signals may be used to enhance engineered adoptive T cell therapy for patients. |
| Author | Ruskin, Susan L Burnett, Madison G Greenberg, Philip D Bates, Breanna M Oda, Shannon K Anderson, Kristin G Rodgers Suarez, Magdalia |
| AuthorAffiliation | 1 Clinical Research , Fred Hutchinson Cancer Research Center , Seattle , Washington , USA 2 Immunology , University of Washington School of Medicine , Seattle , Washington , USA 3 Ben Towne Center for Childhood Cancer Research , Seattle Children's Research Institute , Seattle , Washington , USA |
| AuthorAffiliation_xml | – name: 2 Immunology , University of Washington School of Medicine , Seattle , Washington , USA – name: 3 Ben Towne Center for Childhood Cancer Research , Seattle Children's Research Institute , Seattle , Washington , USA – name: 1 Clinical Research , Fred Hutchinson Cancer Research Center , Seattle , Washington , USA |
| Author_xml | – sequence: 1 givenname: Kristin G orcidid: 0000-0001-9263-4438 surname: Anderson fullname: Anderson, Kristin G organization: Immunology, University of Washington School of Medicine, Seattle, Washington, USA – sequence: 2 givenname: Shannon K surname: Oda fullname: Oda, Shannon K organization: Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington, USA – sequence: 3 givenname: Breanna M surname: Bates fullname: Bates, Breanna M organization: Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA – sequence: 4 givenname: Madison G surname: Burnett fullname: Burnett, Madison G organization: Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA – sequence: 5 givenname: Magdalia surname: Rodgers Suarez fullname: Rodgers Suarez, Magdalia organization: Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA – sequence: 6 givenname: Susan L surname: Ruskin fullname: Ruskin, Susan L organization: Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA – sequence: 7 givenname: Philip D surname: Greenberg fullname: Greenberg, Philip D email: pgreenberg@fredhutch.org organization: Immunology, University of Washington School of Medicine, Seattle, Washington, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/35264436$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1186/1476-4598-5-50 10.1200/JCO.2014.57.4244 10.1016/j.cell.2018.10.038 10.1002/ijc.2910500308 10.1002/cncr.29481 10.1200/JCO.2016.68.3672 10.1158/1078-0432.CCR-09-0737 10.4049/jimmunol.169.9.4882 10.1126/science.7518614 10.1073/pnas.93.1.136 10.1084/jem.20191166 10.1038/s41590-019-0312-6 10.1172/JCI121491 10.1016/j.immuni.2009.01.001 10.1158/2326-6066.CIR-13-0170 10.1111/j.1600-065X.2011.01063.x 10.1371/journal.pone.0126765 10.1038/cdd.2015.3 10.1016/j.ccell.2015.09.022 10.1016/j.immuni.2018.12.021 10.1038/nrc3144 10.1038/sj.bjc.6601635 10.1038/nature09075 10.1084/jem.187.11.1849 10.1158/2326-6066.CIR-19-0258 10.1038/nm.3541 10.1038/s41577-021-00539-6 10.1016/j.cell.2020.03.039 10.3389/fonc.2015.00117 |
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| Keywords | genital neoplasms, female cell engineering tumor microenvironment immunotherapy, adoptive costimulatory and inhibitory T-Cell receptors |
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| References | Miller, Sen, Al Abosy (R14) 2019; 20 Roth, Li, Blaeschke (R26) 2020; 181 Hassan, Thomas, Alewine (R7) 2016; 34 Motz, Santoro, Wang (R12) 2014; 20 Siddiqui, Schaeuble, Chennupati (R28) 2019; 50 Oda, Anderson, Ravikumar (R13) 2020; 217 Chan, Lai, Slaney (R27) 2021; 21 Beatty, Haas, Maus (R9) 2014; 2 Yamamoto, Lee, Vodnala (R19) 2019; 129 Lheureux, Karakasis, Kohn (R1) 2015; 121 Janát-Amsbury, Yockman, Anderson (R15) 2006; 26 Saoulli, Lee, Cannons (R24) 1998; 187 Kägi, Vignaux, Ledermann (R21) 1994; 265 Anderson, Voillet, Bates (R10) 2019; 7 Gubbels, Belisle, Onda (R3) 2006; 5 Chen, Park, Tumanov (R18) 2010; 465 Vaughan, Coward, Bast (R2) 2011; 11 Chang, Pastan (R4) 1996; 93 Lee, Park, Choi (R23) 2002; 169 Snell, Lin, McPherson (R22) 2011; 244 Le, Wang-Gillam, Picozzi (R8) 2015; 33 Heath, Jayne, O'Leary (R17) 2004; 90 Strasser, Jost, Nagata (R20) 2009; 30 Oh, Choi, Kim (R25) 2015; 10 Cheever, Allison, Ferris (R6) 2009; 15 Stromnes, Schmitt, Hulbert (R16) 2015; 28 Chang, Pastan, Willingham (R5) 1992; 50 Peter, Hadji, Murmann (R11) 2015; 22 Sade-Feldman, Yizhak, Bjorgaard (R29) 2018; 175 Bartkowiak, Curran (R30) 2015; 5 Yamamoto (2025100305172408000_10.3.e003959.19) 2019; 129 2025100305172408000_10.3.e003959.3 2025100305172408000_10.3.e003959.2 Hassan (2025100305172408000_10.3.e003959.7) 2016; 34 2025100305172408000_10.3.e003959.5 2025100305172408000_10.3.e003959.4 Chan (2025100305172408000_10.3.e003959.27) 2021; 21 2025100305172408000_10.3.e003959.6 2025100305172408000_10.3.e003959.9 2025100305172408000_10.3.e003959.8 2025100305172408000_10.3.e003959.17 2025100305172408000_10.3.e003959.18 2025100305172408000_10.3.e003959.16 2025100305172408000_10.3.e003959.14 2025100305172408000_10.3.e003959.11 2025100305172408000_10.3.e003959.12 2025100305172408000_10.3.e003959.10 2025100305172408000_10.3.e003959.30 Janát-Amsbury (2025100305172408000_10.3.e003959.15) 2006; 26 Oda (2025100305172408000_10.3.e003959.13) 2020; 217 2025100305172408000_10.3.e003959.28 2025100305172408000_10.3.e003959.29 2025100305172408000_10.3.e003959.26 2025100305172408000_10.3.e003959.24 2025100305172408000_10.3.e003959.25 2025100305172408000_10.3.e003959.22 2025100305172408000_10.3.e003959.23 Lheureux (2025100305172408000_10.3.e003959.1) 2015; 121 2025100305172408000_10.3.e003959.20 2025100305172408000_10.3.e003959.21 |
| References_xml | – volume: 5 year: 2006 ident: R3 article-title: Mesothelin-MUC16 binding is a high affinity, N-glycan dependent interaction that facilitates peritoneal metastasis of ovarian tumors publication-title: Mol Cancer doi: 10.1186/1476-4598-5-50 – volume: 33 start-page: 1325 year: 2015 ident: R8 article-title: Safety and survival with GVAX pancreas prime and Listeria Monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer publication-title: J Clin Oncol doi: 10.1200/JCO.2014.57.4244 – volume: 175 start-page: 998 year: 2018 ident: R29 article-title: Defining T cell states associated with response to checkpoint immunotherapy in melanoma publication-title: Cell doi: 10.1016/j.cell.2018.10.038 – volume: 26 start-page: 2785 year: 2006 ident: R15 article-title: Comparison of ID8 MOSE and VEGF-modified ID8 cell lines in an immunocompetent animal model for human ovarian cancer publication-title: Anticancer Res – volume: 50 start-page: 373 year: 1992 ident: R5 article-title: Isolation and characterization of a monoclonal antibody, K1, reactive with ovarian cancers and normal mesothelium publication-title: Int J Cancer doi: 10.1002/ijc.2910500308 – volume: 121 start-page: 3203 year: 2015 ident: R1 article-title: Ovarian cancer treatment: the end of empiricism? publication-title: Cancer doi: 10.1002/cncr.29481 – volume: 34 start-page: 4171 year: 2016 ident: R7 article-title: Mesothelin immunotherapy for cancer: ready for prime time? publication-title: J Clin Oncol doi: 10.1200/JCO.2016.68.3672 – volume: 15 start-page: 5323 year: 2009 ident: R6 article-title: The prioritization of cancer antigens: a national cancer Institute pilot project for the acceleration of translational research publication-title: Clin Cancer Res doi: 10.1158/1078-0432.CCR-09-0737 – volume: 169 start-page: 4882 year: 2002 ident: R23 article-title: 4-1BB promotes the survival of CD8+ T lymphocytes by increasing expression of Bcl-xL and Bfl-1 publication-title: J Immunol doi: 10.4049/jimmunol.169.9.4882 – volume: 265 start-page: 528 year: 1994 ident: R21 article-title: Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicity publication-title: Science doi: 10.1126/science.7518614 – volume: 93 start-page: 136 year: 1996 ident: R4 article-title: Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.93.1.136 – volume: 217 year: 2020 ident: R13 article-title: A Fas-4-1BB fusion protein converts a death to a pro-survival signal and enhances T cell therapy publication-title: J Exp Med doi: 10.1084/jem.20191166 – volume: 20 start-page: 326 year: 2019 ident: R14 article-title: Subsets of exhausted CD8+ T cells differentially mediate tumor control and respond to checkpoint blockade publication-title: Nat Immunol doi: 10.1038/s41590-019-0312-6 – volume: 129 start-page: 1551 year: 2019 ident: R19 article-title: T cells genetically engineered to overcome death signaling enhance adoptive cancer immunotherapy publication-title: J Clin Invest doi: 10.1172/JCI121491 – volume: 30 start-page: 180 year: 2009 ident: R20 article-title: The many roles of Fas receptor signaling in the immune system publication-title: Immunity doi: 10.1016/j.immuni.2009.01.001 – volume: 2 start-page: 112 year: 2014 ident: R9 article-title: Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies publication-title: Cancer Immunol Res doi: 10.1158/2326-6066.CIR-13-0170 – volume: 244 start-page: 197 year: 2011 ident: R22 article-title: T‐cell intrinsic effects of GITR and 4-1BB during viral infection and cancer immunotherapy publication-title: Immunol Rev doi: 10.1111/j.1600-065X.2011.01063.x – volume: 10 year: 2015 ident: R25 article-title: 4-1BB signaling enhances primary and secondary population expansion of CD8+ T cells by maximizing autocrine IL-2/IL-2 receptor signaling publication-title: PLoS One doi: 10.1371/journal.pone.0126765 – volume: 22 start-page: 549 year: 2015 ident: R11 article-title: The role of CD95 and CD95 ligand in cancer publication-title: Cell Death Differ doi: 10.1038/cdd.2015.3 – volume: 28 start-page: 638 year: 2015 ident: R16 article-title: T cells engineered against a native antigen can Surmount immunologic and physical barriers to treat pancreatic ductal adenocarcinoma publication-title: Cancer Cell doi: 10.1016/j.ccell.2015.09.022 – volume: 50 start-page: 195 year: 2019 ident: R28 article-title: Intratumoral Tcf1+PD-1+CD8+ T Cells with Stem-like Properties Promote Tumor Control in Response to Vaccination and Checkpoint Blockade Immunotherapy publication-title: Immunity doi: 10.1016/j.immuni.2018.12.021 – volume: 11 start-page: 719 year: 2011 ident: R2 article-title: Rethinking ovarian cancer: recommendations for improving outcomes publication-title: Nat Rev Cancer doi: 10.1038/nrc3144 – volume: 90 start-page: 1437 year: 2004 ident: R17 article-title: Tumour-Induced apoptosis in human mesothelial cells: a mechanism of peritoneal invasion by Fas Ligand/Fas interaction publication-title: Br J Cancer doi: 10.1038/sj.bjc.6601635 – volume: 465 start-page: 492 year: 2010 ident: R18 article-title: CD95 promotes tumour growth publication-title: Nature doi: 10.1038/nature09075 – volume: 187 start-page: 1849 year: 1998 ident: R24 article-title: CD28-independent, TRAF2-dependent costimulation of resting T cells by 4-1BB ligand publication-title: J Exp Med doi: 10.1084/jem.187.11.1849 – volume: 7 start-page: 1412 year: 2019 ident: R10 article-title: Engineered adoptive T-cell therapy prolongs survival in a preclinical model of advanced-stage ovarian cancer publication-title: Cancer Immunol Res doi: 10.1158/2326-6066.CIR-19-0258 – volume: 20 start-page: 607 year: 2014 ident: R12 article-title: Tumor endothelium FasL establishes a selective immune barrier promoting tolerance in tumors publication-title: Nat Med doi: 10.1038/nm.3541 – volume: 21 start-page: 769 year: 2021 ident: R27 article-title: Cellular networks controlling T cell persistence in adoptive cell therapy publication-title: Nat Rev Immunol doi: 10.1038/s41577-021-00539-6 – volume: 181 start-page: 728 year: 2020 ident: R26 article-title: Pooled knockin targeting for genome engineering of cellular immunotherapies publication-title: Cell doi: 10.1016/j.cell.2020.03.039 – volume: 5 year: 2015 ident: R30 article-title: 4-1BB agonists: multi-potent potentiators of tumor immunity publication-title: Front Oncol doi: 10.3389/fonc.2015.00117 – ident: 2025100305172408000_10.3.e003959.20 doi: 10.1016/j.immuni.2009.01.001 – volume: 217 year: 2020 ident: 2025100305172408000_10.3.e003959.13 article-title: A Fas-4-1BB fusion protein converts a death to a pro-survival signal and enhances T cell therapy publication-title: J Exp Med doi: 10.1084/jem.20191166 – ident: 2025100305172408000_10.3.e003959.12 doi: 10.1038/nm.3541 – ident: 2025100305172408000_10.3.e003959.18 doi: 10.1038/nature09075 – volume: 34 start-page: 4171 year: 2016 ident: 2025100305172408000_10.3.e003959.7 article-title: Mesothelin immunotherapy for cancer: ready for prime time? publication-title: J Clin Oncol doi: 10.1200/JCO.2016.68.3672 – ident: 2025100305172408000_10.3.e003959.2 doi: 10.1038/nrc3144 – ident: 2025100305172408000_10.3.e003959.6 doi: 10.1158/1078-0432.CCR-09-0737 – ident: 2025100305172408000_10.3.e003959.28 doi: 10.1016/j.immuni.2018.12.021 – ident: 2025100305172408000_10.3.e003959.22 doi: 10.1111/j.1600-065X.2011.01063.x – ident: 2025100305172408000_10.3.e003959.26 doi: 10.1016/j.cell.2020.03.039 – volume: 121 start-page: 3203 year: 2015 ident: 2025100305172408000_10.3.e003959.1 article-title: Ovarian cancer treatment: the end of empiricism? publication-title: Cancer doi: 10.1002/cncr.29481 – ident: 2025100305172408000_10.3.e003959.23 doi: 10.4049/jimmunol.169.9.4882 – ident: 2025100305172408000_10.3.e003959.16 doi: 10.1016/j.ccell.2015.09.022 – ident: 2025100305172408000_10.3.e003959.29 doi: 10.1016/j.cell.2018.10.038 – ident: 2025100305172408000_10.3.e003959.21 doi: 10.1126/science.7518614 – ident: 2025100305172408000_10.3.e003959.10 doi: 10.1158/2326-6066.CIR-19-0258 – ident: 2025100305172408000_10.3.e003959.30 doi: 10.3389/fonc.2015.00117 – ident: 2025100305172408000_10.3.e003959.3 doi: 10.1186/1476-4598-5-50 – volume: 26 start-page: 2785 year: 2006 ident: 2025100305172408000_10.3.e003959.15 article-title: Comparison of ID8 MOSE and VEGF-modified ID8 cell lines in an immunocompetent animal model for human ovarian cancer publication-title: Anticancer Res – ident: 2025100305172408000_10.3.e003959.8 doi: 10.1200/JCO.2014.57.4244 – ident: 2025100305172408000_10.3.e003959.9 doi: 10.1158/2326-6066.CIR-13-0170 – ident: 2025100305172408000_10.3.e003959.4 doi: 10.1073/pnas.93.1.136 – ident: 2025100305172408000_10.3.e003959.11 doi: 10.1038/cdd.2015.3 – ident: 2025100305172408000_10.3.e003959.14 doi: 10.1038/s41590-019-0312-6 – ident: 2025100305172408000_10.3.e003959.24 doi: 10.1084/jem.187.11.1849 – ident: 2025100305172408000_10.3.e003959.17 doi: 10.1038/sj.bjc.6601635 – ident: 2025100305172408000_10.3.e003959.25 doi: 10.1371/journal.pone.0126765 – volume: 21 start-page: 769 year: 2021 ident: 2025100305172408000_10.3.e003959.27 article-title: Cellular networks controlling T cell persistence in adoptive cell therapy publication-title: Nat Rev Immunol doi: 10.1038/s41577-021-00539-6 – ident: 2025100305172408000_10.3.e003959.5 doi: 10.1002/ijc.2910500308 – volume: 129 start-page: 1551 year: 2019 ident: 2025100305172408000_10.3.e003959.19 article-title: T cells genetically engineered to overcome death signaling enhance adoptive cancer immunotherapy publication-title: J Clin Invest doi: 10.1172/JCI121491 |
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| Snippet | BackgroundIn the USA, more than 50% of patients with ovarian cancer die within 5 years of diagnosis, highlighting the need for therapeutic innovations.... In the USA, more than 50% of patients with ovarian cancer die within 5 years of diagnosis, highlighting the need for therapeutic innovations. Mesothelin (MSLN)... Background In the USA, more than 50% of patients with ovarian cancer die within 5 years of diagnosis, highlighting the need for therapeutic innovations.... |
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| SubjectTerms | Cancer cell engineering costimulatory and inhibitory T-Cell receptors Cytokines Genital cancers genital neoplasms, female Immune Cell Therapies and Immune Cell Engineering Immunotherapy immunotherapy, adoptive Lymphocytes Ovarian cancer T cell receptors tumor microenvironment Tumors |
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| Title | Engineering adoptive T cell therapy to co-opt Fas ligand-mediated death signaling in ovarian cancer enhances therapeutic efficacy |
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