Engineering a Smart Agent for Enhanced Immunotherapy Effect by Simultaneously Blocking PD‐L1 and CTLA‐4

Combinations of immune checkpoint therapies show encouraging results in the treatment of many human cancers. However, the higher costs and greater side effects of such combinations compared with single‐agent immunotherapies limit their further applications. In this work, a novel smart agent, KN046@1...

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Published in:Advanced science Vol. 8; no. 20; pp. e2102500 - n/a
Main Authors: Jiang, Chunjuan, Zhang, Le, Xu, Xiaoping, Qi, Ming, Zhang, Jianping, He, Simin, Tian, Qiwei, Song, Shaoli
Format: Journal Article
Language:English
Published: Germany John Wiley & Sons, Inc 01.10.2021
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Abstract Combinations of immune checkpoint therapies show encouraging results in the treatment of many human cancers. However, the higher costs and greater side effects of such combinations compared with single‐agent immunotherapies limit their further applications. In this work, a novel smart agent, KN046@19F‐ZIF‐8, is developed to overcome these limitations. KN046 is a novel recombinant humanized PD‐L1/CTLA‐4 bispecific single‐domain antibody‐Fc fusion protein, which can bind to both PD‐L1 and CTLA‐4 effectively. ZIF‐8 is a smart delivery system, which can safely and effectively deliver KN406 to a tumor. In vitro and in vivo results demonstrate that the smart agent KN046@19F‐ZIF‐8 not only improves the immune response rate of the antibody drug in treatment of tumors but also reduces its toxic side effects, thereby achieving excellent antitumor efficacy. This study provides an engineering strategy for clinical applications of a more effective immunotherapy. A novel smart agent is engineered by coating a tumor microenvironment responsive ZIF‐8 on the novel recombinant humanized PD‐L1/CTLA‐4 bispecific single‐domain antibody‐Fc fusion protein to overcome the higher costs and greater side effects of single‐agent immunotherapies.
AbstractList Combinations of immune checkpoint therapies show encouraging results in the treatment of many human cancers. However, the higher costs and greater side effects of such combinations compared with single-agent immunotherapies limit their further applications. In this work, a novel smart agent, KN046@19 F-ZIF-8, is developed to overcome these limitations. KN046 is a novel recombinant humanized PD-L1/CTLA-4 bispecific single-domain antibody-Fc fusion protein, which can bind to both PD-L1 and CTLA-4 effectively. ZIF-8 is a smart delivery system, which can safely and effectively deliver KN406 to a tumor. In vitro and in vivo results demonstrate that the smart agent KN046@19 F-ZIF-8 not only improves the immune response rate of the antibody drug in treatment of tumors but also reduces its toxic side effects, thereby achieving excellent antitumor efficacy. This study provides an engineering strategy for clinical applications of a more effective immunotherapy.Combinations of immune checkpoint therapies show encouraging results in the treatment of many human cancers. However, the higher costs and greater side effects of such combinations compared with single-agent immunotherapies limit their further applications. In this work, a novel smart agent, KN046@19 F-ZIF-8, is developed to overcome these limitations. KN046 is a novel recombinant humanized PD-L1/CTLA-4 bispecific single-domain antibody-Fc fusion protein, which can bind to both PD-L1 and CTLA-4 effectively. ZIF-8 is a smart delivery system, which can safely and effectively deliver KN406 to a tumor. In vitro and in vivo results demonstrate that the smart agent KN046@19 F-ZIF-8 not only improves the immune response rate of the antibody drug in treatment of tumors but also reduces its toxic side effects, thereby achieving excellent antitumor efficacy. This study provides an engineering strategy for clinical applications of a more effective immunotherapy.
Combinations of immune checkpoint therapies show encouraging results in the treatment of many human cancers. However, the higher costs and greater side effects of such combinations compared with single‐agent immunotherapies limit their further applications. In this work, a novel smart agent, KN046@19F‐ZIF‐8, is developed to overcome these limitations. KN046 is a novel recombinant humanized PD‐L1/CTLA‐4 bispecific single‐domain antibody‐Fc fusion protein, which can bind to both PD‐L1 and CTLA‐4 effectively. ZIF‐8 is a smart delivery system, which can safely and effectively deliver KN406 to a tumor. In vitro and in vivo results demonstrate that the smart agent KN046@19F‐ZIF‐8 not only improves the immune response rate of the antibody drug in treatment of tumors but also reduces its toxic side effects, thereby achieving excellent antitumor efficacy. This study provides an engineering strategy for clinical applications of a more effective immunotherapy.
Combinations of immune checkpoint therapies show encouraging results in the treatment of many human cancers. However, the higher costs and greater side effects of such combinations compared with single‐agent immunotherapies limit their further applications. In this work, a novel smart agent, KN046@19F‐ZIF‐8, is developed to overcome these limitations. KN046 is a novel recombinant humanized PD‐L1/CTLA‐4 bispecific single‐domain antibody‐Fc fusion protein, which can bind to both PD‐L1 and CTLA‐4 effectively. ZIF‐8 is a smart delivery system, which can safely and effectively deliver KN406 to a tumor. In vitro and in vivo results demonstrate that the smart agent KN046@19F‐ZIF‐8 not only improves the immune response rate of the antibody drug in treatment of tumors but also reduces its toxic side effects, thereby achieving excellent antitumor efficacy. This study provides an engineering strategy for clinical applications of a more effective immunotherapy. A novel smart agent is engineered by coating a tumor microenvironment responsive ZIF‐8 on the novel recombinant humanized PD‐L1/CTLA‐4 bispecific single‐domain antibody‐Fc fusion protein to overcome the higher costs and greater side effects of single‐agent immunotherapies.
Abstract Combinations of immune checkpoint therapies show encouraging results in the treatment of many human cancers. However, the higher costs and greater side effects of such combinations compared with single‐agent immunotherapies limit their further applications. In this work, a novel smart agent, KN046@19F‐ZIF‐8, is developed to overcome these limitations. KN046 is a novel recombinant humanized PD‐L1/CTLA‐4 bispecific single‐domain antibody‐Fc fusion protein, which can bind to both PD‐L1 and CTLA‐4 effectively. ZIF‐8 is a smart delivery system, which can safely and effectively deliver KN406 to a tumor. In vitro and in vivo results demonstrate that the smart agent KN046@19F‐ZIF‐8 not only improves the immune response rate of the antibody drug in treatment of tumors but also reduces its toxic side effects, thereby achieving excellent antitumor efficacy. This study provides an engineering strategy for clinical applications of a more effective immunotherapy.
Combinations of immune checkpoint therapies show encouraging results in the treatment of many human cancers. However, the higher costs and greater side effects of such combinations compared with single‐agent immunotherapies limit their further applications. In this work, a novel smart agent, KN046@ 19 F‐ZIF‐8, is developed to overcome these limitations. KN046 is a novel recombinant humanized PD‐L1/CTLA‐4 bispecific single‐domain antibody‐Fc fusion protein, which can bind to both PD‐L1 and CTLA‐4 effectively. ZIF‐8 is a smart delivery system, which can safely and effectively deliver KN406 to a tumor. In vitro and in vivo results demonstrate that the smart agent KN046@ 19 F‐ZIF‐8 not only improves the immune response rate of the antibody drug in treatment of tumors but also reduces its toxic side effects, thereby achieving excellent antitumor efficacy. This study provides an engineering strategy for clinical applications of a more effective immunotherapy.
Combinations of immune checkpoint therapies show encouraging results in the treatment of many human cancers. However, the higher costs and greater side effects of such combinations compared with single‐agent immunotherapies limit their further applications. In this work, a novel smart agent, KN046@19F‐ZIF‐8, is developed to overcome these limitations. KN046 is a novel recombinant humanized PD‐L1/CTLA‐4 bispecific single‐domain antibody‐Fc fusion protein, which can bind to both PD‐L1 and CTLA‐4 effectively. ZIF‐8 is a smart delivery system, which can safely and effectively deliver KN406 to a tumor. In vitro and in vivo results demonstrate that the smart agent KN046@19F‐ZIF‐8 not only improves the immune response rate of the antibody drug in treatment of tumors but also reduces its toxic side effects, thereby achieving excellent antitumor efficacy. This study provides an engineering strategy for clinical applications of a more effective immunotherapy. A novel smart agent is engineered by coating a tumor microenvironment responsive ZIF‐8 on the novel recombinant humanized PD‐L1/CTLA‐4 bispecific single‐domain antibody‐Fc fusion protein to overcome the higher costs and greater side effects of single‐agent immunotherapies.
Combinations of immune checkpoint therapies show encouraging results in the treatment of many human cancers. However, the higher costs and greater side effects of such combinations compared with single-agent immunotherapies limit their further applications. In this work, a novel smart agent, KN046@ F-ZIF-8, is developed to overcome these limitations. KN046 is a novel recombinant humanized PD-L1/CTLA-4 bispecific single-domain antibody-Fc fusion protein, which can bind to both PD-L1 and CTLA-4 effectively. ZIF-8 is a smart delivery system, which can safely and effectively deliver KN406 to a tumor. In vitro and in vivo results demonstrate that the smart agent KN046@ F-ZIF-8 not only improves the immune response rate of the antibody drug in treatment of tumors but also reduces its toxic side effects, thereby achieving excellent antitumor efficacy. This study provides an engineering strategy for clinical applications of a more effective immunotherapy.
Author Tian, Qiwei
Xu, Xiaoping
Zhang, Le
Song, Shaoli
Zhang, Jianping
Jiang, Chunjuan
Qi, Ming
He, Simin
AuthorAffiliation 3 Shanghai Engineering Research Center of Molecular Imaging Probes Shanghai 200032 China
2 Center for Biomedical Imaging Fudan University Shanghai 200032 China
5 Shanghai Key Laboratory of Molecular Imaging Shanghai University of Medicine and Health Sciences Shanghai 201318 China
4 Department of Research and Development Shanghai Proton and Heavy Ion Center Shanghai 201321 China
1 Department of Nuclear Medicine Fudan University Shanghai Cancer Center Shanghai 200032 China
AuthorAffiliation_xml – name: 1 Department of Nuclear Medicine Fudan University Shanghai Cancer Center Shanghai 200032 China
– name: 4 Department of Research and Development Shanghai Proton and Heavy Ion Center Shanghai 201321 China
– name: 5 Shanghai Key Laboratory of Molecular Imaging Shanghai University of Medicine and Health Sciences Shanghai 201318 China
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/34473430$$D View this record in MEDLINE/PubMed
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Cites_doi 10.2174/0929867324666170804143706
10.1021/acsami.0c00302
10.1158/0008-5472.CAN-16-3346
10.1021/acsnano.5b06759
10.1056/NEJMoa1910836
10.1158/0008-5472.CAN-15-1707
10.3892/mmr.2014.2914
10.1002/advs.201700648
10.1021/cr500286d
10.1002/cncr.33133
10.1182/blood-2005-05-1864
10.1158/1078-0432.CCR-18-2407
10.1016/j.immuni.2019.10.009
10.1016/S0140-6736(20)30417-7
10.1200/JCO.2008.17.1496
10.1038/s41572-020-0160-6
10.1002/anie.201308500
10.1073/pnas.0707715105
10.1007/s00330-018-5904-2
10.1016/j.vetimm.2006.12.002
10.7150/thno.38339
10.1002/anie.201702114
10.1039/C6CC06616J
10.1002/adma.201805148
10.1038/sj.cdd.4402103
10.1038/s41571-020-0413-z
10.1021/nn406590q
10.1016/j.biomaterials.2018.02.022
10.1002/anie.201700426
10.1007/s00330-018-5814-3
10.3390/molecules25133102
10.1021/acsami.7b16522
10.1186/s13046-019-1259-z
10.1111/1346-8138.15514
10.1080/14712598.2019.1592155
10.1002/med.21727
10.1126/science.1251102
10.1007/978-3-030-35723-8_4
10.1021/acs.biomac.5b00800
10.1021/cb500986w
10.1126/science.aaa6204
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Keywords immunotherapies
granzyme B probes
positron emission tomography/computed tomography imaging
ZIF-8
19F MRI
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References 2015; 16
2018; 162
2019; 51
2019; 31
2015; 11
2015; 10
2020; 126
2020; 17
2016; 10
2020; 39
2016; 76
2019; 38
2019; 19
2016; 52
2008; 105
2020; 12
2015; 348
2020; 10
2019; 381
2007; 14
2020; 6
2018; 5
2007; 116
2015; 115
2020; 395
2017; 77
2019; 26
2017; 56
2019; 25
2005; 106
2002; 106
2008; 26
2020; 47
2019; 29
2020; 25
2014; 8
2018; 10
2021; 41
2020; 1224
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2014; 344
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References_xml – volume: 39
  start-page: 220
  year: 2020
  publication-title: Rev. Esp. Med. Nucl. Imagen Mol.
– volume: 25
  start-page: 1196
  year: 2019
  publication-title: Clin. Cancer Res.
– volume: 11
  start-page: 1566
  year: 2015
  publication-title: Mol. Med. Rep.
– volume: 126
  start-page: 4926
  year: 2020
  publication-title: Cancer
– volume: 10
  start-page: 864
  year: 2015
  publication-title: ACS Chem. Biol.
– volume: 77
  start-page: 2318
  year: 2017
  publication-title: Cancer Res.
– volume: 12
  start-page: 8050
  year: 2020
  publication-title: ACS Appl. Mater. Interfaces
– volume: 10
  start-page: 1708
  year: 2020
  publication-title: Theranostics
– volume: 106
  start-page: 3097
  year: 2005
  publication-title: Blood
– volume: 38
  start-page: 255
  year: 2019
  publication-title: J. Exp. Clin. Cancer Res.
– volume: 29
  start-page: 2490
  year: 2019
  publication-title: Eur. Radiol.
– volume: 19
  start-page: 423
  year: 2019
  publication-title: Expert Opin. Biol. Ther.
– volume: 56
  start-page: 5812
  year: 2017
  publication-title: Angew. Chem., Int. Ed.
– volume: 14
  start-page: 641
  year: 2007
  publication-title: Cell Death Differ.
– volume: 105
  year: 2008
  publication-title: Proc. Natl. Acad. Sci. USA
– volume: 381
  start-page: 1535
  year: 2019
  publication-title: N. Engl. J. Med.
– volume: 53
  start-page: 1008
  year: 2014
  publication-title: Angew. Chem., Int. Ed.
– volume: 26
  start-page: 3009
  year: 2019
  publication-title: Curr. Med. Chem.
– volume: 162
  start-page: 132
  year: 2018
  publication-title: Biomaterials
– volume: 8
  start-page: 2812
  year: 2014
  publication-title: ACS Nano
– volume: 31
  year: 2019
  publication-title: Adv. Mater.
– volume: 56
  start-page: 6440
  year: 2017
  publication-title: Angew. Chem., Int. Ed.
– volume: 1224
  start-page: 53
  year: 2020
  publication-title: Adv. Exp. Med. Biol.
– volume: 16
  start-page: 2827
  year: 2015
  publication-title: Biomacromolecules
– volume: 47
  start-page: 1257
  year: 2020
  publication-title: J. Dermatol.
– volume: 10
  start-page: 2328
  year: 2018
  publication-title: ACS Appl. Mater. Interfaces
– volume: 76
  start-page: 73
  year: 2016
  publication-title: Cancer Res.
– volume: 41
  start-page: 156
  year: 2021
  publication-title: Med. Res. Rev.
– volume: 52
  year: 2016
  publication-title: Chem. Commun.
– volume: 10
  start-page: 1355
  year: 2016
  publication-title: ACS Nano
– volume: 106
  start-page: 14
  year: 2002
  publication-title: Rev. Med. Chir. Soc. Med. Nat. Iasi
– volume: 116
  start-page: 69
  year: 2007
  publication-title: Vet. Immunol. Immunopathol.
– volume: 348
  start-page: 74
  year: 2015
  publication-title: Science
– volume: 6
  start-page: 38
  year: 2020
  publication-title: Nat. Rev. Dis. Primers
– volume: 395
  start-page: 1558
  year: 2020
  publication-title: Lancet
– volume: 5
  year: 2018
  publication-title: Adv. Sci. (Weinh)
– volume: 51
  start-page: 1028
  year: 2019
  publication-title: Immunity
– volume: 17
  start-page: 725
  year: 2020
  publication-title: Nat. Rev. Clin. Oncol.
– volume: 25
  start-page: 3102
  year: 2020
  publication-title: Molecules
– volume: 29
  start-page: 4294
  year: 2019
  publication-title: Eur. Radiol.
– volume: 26
  start-page: 4746
  year: 2008
  publication-title: J. Clin. Oncol.
– volume: 344
  start-page: 641
  year: 2014
  publication-title: Science
– volume: 115
  start-page: 1106
  year: 2015
  publication-title: Chem. Rev.
– ident: e_1_2_8_2_1
  doi: 10.2174/0929867324666170804143706
– ident: e_1_2_8_16_1
  doi: 10.1021/acsami.0c00302
– ident: e_1_2_8_34_1
  doi: 10.1158/0008-5472.CAN-16-3346
– ident: e_1_2_8_26_1
  doi: 10.1021/acsnano.5b06759
– ident: e_1_2_8_8_1
  doi: 10.1056/NEJMoa1910836
– ident: e_1_2_8_35_1
  doi: 10.1158/0008-5472.CAN-15-1707
– ident: e_1_2_8_43_1
  doi: 10.3892/mmr.2014.2914
– ident: e_1_2_8_14_1
  doi: 10.1002/advs.201700648
– ident: e_1_2_8_21_1
  doi: 10.1021/cr500286d
– ident: e_1_2_8_1_1
  doi: 10.1002/cncr.33133
– ident: e_1_2_8_41_1
  doi: 10.1182/blood-2005-05-1864
– volume: 106
  start-page: 14
  year: 2002
  ident: e_1_2_8_30_1
  publication-title: Rev. Med. Chir. Soc. Med. Nat. Iasi
– ident: e_1_2_8_36_1
  doi: 10.1158/1078-0432.CCR-18-2407
– volume: 39
  start-page: 220
  year: 2020
  ident: e_1_2_8_28_1
  publication-title: Rev. Esp. Med. Nucl. Imagen Mol.
– ident: e_1_2_8_38_1
  doi: 10.1016/j.immuni.2019.10.009
– ident: e_1_2_8_3_1
  doi: 10.1016/S0140-6736(20)30417-7
– ident: e_1_2_8_29_1
  doi: 10.1200/JCO.2008.17.1496
– ident: e_1_2_8_10_1
  doi: 10.1038/s41572-020-0160-6
– ident: e_1_2_8_20_1
  doi: 10.1002/anie.201308500
– ident: e_1_2_8_32_1
  doi: 10.1073/pnas.0707715105
– ident: e_1_2_8_27_1
  doi: 10.1007/s00330-018-5904-2
– ident: e_1_2_8_42_1
  doi: 10.1016/j.vetimm.2006.12.002
– ident: e_1_2_8_18_1
  doi: 10.7150/thno.38339
– ident: e_1_2_8_23_1
  doi: 10.1002/anie.201702114
– ident: e_1_2_8_11_1
  doi: 10.1039/C6CC06616J
– ident: e_1_2_8_13_1
  doi: 10.1002/adma.201805148
– ident: e_1_2_8_31_1
  doi: 10.1038/sj.cdd.4402103
– ident: e_1_2_8_4_1
  doi: 10.1038/s41571-020-0413-z
– ident: e_1_2_8_12_1
  doi: 10.1021/nn406590q
– ident: e_1_2_8_15_1
  doi: 10.1016/j.biomaterials.2018.02.022
– ident: e_1_2_8_19_1
  doi: 10.1002/anie.201700426
– ident: e_1_2_8_17_1
  doi: 10.1007/s00330-018-5814-3
– ident: e_1_2_8_33_1
  doi: 10.3390/molecules25133102
– ident: e_1_2_8_22_1
  doi: 10.1021/acsami.7b16522
– ident: e_1_2_8_6_1
  doi: 10.1186/s13046-019-1259-z
– ident: e_1_2_8_5_1
  doi: 10.1111/1346-8138.15514
– ident: e_1_2_8_7_1
  doi: 10.1080/14712598.2019.1592155
– ident: e_1_2_8_39_1
  doi: 10.1002/med.21727
– ident: e_1_2_8_37_1
  doi: 10.1126/science.1251102
– ident: e_1_2_8_40_1
  doi: 10.1007/978-3-030-35723-8_4
– ident: e_1_2_8_25_1
  doi: 10.1021/acs.biomac.5b00800
– ident: e_1_2_8_24_1
  doi: 10.1021/cb500986w
– ident: e_1_2_8_9_1
  doi: 10.1126/science.aaa6204
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Snippet Combinations of immune checkpoint therapies show encouraging results in the treatment of many human cancers. However, the higher costs and greater side effects...
Abstract Combinations of immune checkpoint therapies show encouraging results in the treatment of many human cancers. However, the higher costs and greater...
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SubjectTerms 19F MRI
Animals
Antibodies
Antibodies, Bispecific - chemistry
Antibodies, Bispecific - immunology
Antibodies, Bispecific - pharmacology
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
B7-H1 Antigen - antagonists & inhibitors
B7-H1 Antigen - genetics
B7-H1 Antigen - immunology
Cancer
Cell Line, Tumor
Cell Proliferation - drug effects
CTLA-4 Antigen - antagonists & inhibitors
CTLA-4 Antigen - genetics
CTLA-4 Antigen - immunology
Efficiency
FDA approval
Fluorine
granzyme B probes
Humans
Immune Checkpoint Inhibitors - pharmacology
immunotherapies
Immunotherapy
Melanoma
Mice
Nanoparticles
Neoplasms - genetics
Neoplasms - immunology
Neoplasms - therapy
Physiology
positron emission tomography/computed tomography imaging
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - immunology
Recombinant Fusion Proteins - pharmacology
Scanning electron microscopy
Single-Domain Antibodies - chemistry
Single-Domain Antibodies - immunology
Single-Domain Antibodies - pharmacology
Tumors
Xenograft Model Antitumor Assays
ZIF‐8
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Title Engineering a Smart Agent for Enhanced Immunotherapy Effect by Simultaneously Blocking PD‐L1 and CTLA‐4
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