Successful targeting of PD-1/PD-L1 with chimeric antigen receptor-natural killer cells and nivolumab in a humanized mouse cancer model
In recent decades, chimeric antigen receptor (CAR)–engineered immune effector cells have demonstrated promising antileukemic activity. Nevertheless, their efficacy remains unsatisfactory on solid cancers, plausibly due to the influence of tumor microenvironments (TME). In a novel mouse cancer model...
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| Published in | Science advances Vol. 8; no. 47; p. eadd1187 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Association for the Advancement of Science
25.11.2022
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| Subjects | |
| Online Access | Get full text |
| ISSN | 2375-2548 2375-2548 |
| DOI | 10.1126/sciadv.add1187 |
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| Abstract | In recent decades, chimeric antigen receptor (CAR)–engineered immune effector cells have demonstrated promising antileukemic activity. Nevertheless, their efficacy remains unsatisfactory on solid cancers, plausibly due to the influence of tumor microenvironments (TME). In a novel mouse cancer model with a humanized immune system, tumor-infiltrating immunosuppressive leukocytes and exhausted programmed death protein-1 (PD-1)
high
T cells were found, which better mimic patient TME, allowing the screening and assessment of immune therapeutics. Particularly, membrane-bound programmed death ligand 1 (PD-L1) level was elevated on a tumor cell surface, which serves as an attractive target for natural killer (NK) cell–mediated therapy. Hematopoietic stem cell–derived CAR-NK (CAR pNK) cells targeting the PD-L1 showed enhanced in vitro and in vivo anti-solid tumor function. The CAR pNK cells and nivolumab resulted in a synergistic anti-solid tumor response. Together, our study highlights a robust platform to develop and evaluate the antitumor efficacy and safety of previously unexplored therapeutic regimens.
Stem cell-derived chimeric antigen receptor-natural killer cells inhibit solid tumor growth in humanized mice. |
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| AbstractList | In recent decades, chimeric antigen receptor (CAR)-engineered immune effector cells have demonstrated promising antileukemic activity. Nevertheless, their efficacy remains unsatisfactory on solid cancers, plausibly due to the influence of tumor microenvironments (TME). In a novel mouse cancer model with a humanized immune system, tumor-infiltrating immunosuppressive leukocytes and exhausted programmed death protein-1 (PD-1)high T cells were found, which better mimic patient TME, allowing the screening and assessment of immune therapeutics. Particularly, membrane-bound programmed death ligand 1 (PD-L1) level was elevated on a tumor cell surface, which serves as an attractive target for natural killer (NK) cell-mediated therapy. Hematopoietic stem cell-derived CAR-NK (CAR pNK) cells targeting the PD-L1 showed enhanced in vitro and in vivo anti-solid tumor function. The CAR pNK cells and nivolumab resulted in a synergistic anti-solid tumor response. Together, our study highlights a robust platform to develop and evaluate the antitumor efficacy and safety of previously unexplored therapeutic regimens.In recent decades, chimeric antigen receptor (CAR)-engineered immune effector cells have demonstrated promising antileukemic activity. Nevertheless, their efficacy remains unsatisfactory on solid cancers, plausibly due to the influence of tumor microenvironments (TME). In a novel mouse cancer model with a humanized immune system, tumor-infiltrating immunosuppressive leukocytes and exhausted programmed death protein-1 (PD-1)high T cells were found, which better mimic patient TME, allowing the screening and assessment of immune therapeutics. Particularly, membrane-bound programmed death ligand 1 (PD-L1) level was elevated on a tumor cell surface, which serves as an attractive target for natural killer (NK) cell-mediated therapy. Hematopoietic stem cell-derived CAR-NK (CAR pNK) cells targeting the PD-L1 showed enhanced in vitro and in vivo anti-solid tumor function. The CAR pNK cells and nivolumab resulted in a synergistic anti-solid tumor response. Together, our study highlights a robust platform to develop and evaluate the antitumor efficacy and safety of previously unexplored therapeutic regimens. In recent decades, chimeric antigen receptor (CAR)–engineered immune effector cells have demonstrated promising antileukemic activity. Nevertheless, their efficacy remains unsatisfactory on solid cancers, plausibly due to the influence of tumor microenvironments (TME). In a novel mouse cancer model with a humanized immune system, tumor-infiltrating immunosuppressive leukocytes and exhausted programmed death protein-1 (PD-1) high T cells were found, which better mimic patient TME, allowing the screening and assessment of immune therapeutics. Particularly, membrane-bound programmed death ligand 1 (PD-L1) level was elevated on a tumor cell surface, which serves as an attractive target for natural killer (NK) cell–mediated therapy. Hematopoietic stem cell–derived CAR-NK (CAR pNK) cells targeting the PD-L1 showed enhanced in vitro and in vivo anti-solid tumor function. The CAR pNK cells and nivolumab resulted in a synergistic anti-solid tumor response. Together, our study highlights a robust platform to develop and evaluate the antitumor efficacy and safety of previously unexplored therapeutic regimens. Stem cell-derived chimeric antigen receptor-natural killer cells inhibit solid tumor growth in humanized mice. In recent decades, chimeric antigen receptor (CAR)-engineered immune effector cells have demonstrated promising antileukemic activity. Nevertheless, their efficacy remains unsatisfactory on solid cancers, plausibly due to the influence of tumor microenvironments (TME). In a novel mouse cancer model with a humanized immune system, tumor-infiltrating immunosuppressive leukocytes and exhausted programmed death protein-1 (PD-1) T cells were found, which better mimic patient TME, allowing the screening and assessment of immune therapeutics. Particularly, membrane-bound programmed death ligand 1 (PD-L1) level was elevated on a tumor cell surface, which serves as an attractive target for natural killer (NK) cell-mediated therapy. Hematopoietic stem cell-derived CAR-NK (CAR pNK) cells targeting the PD-L1 showed enhanced in vitro and in vivo anti-solid tumor function. The CAR pNK cells and nivolumab resulted in a synergistic anti-solid tumor response. Together, our study highlights a robust platform to develop and evaluate the antitumor efficacy and safety of previously unexplored therapeutic regimens. |
| Author | Ong, Jessica Kai Lin Cheng, Jia Ying Chen, Qingfeng Fong, Shin Yie Liu, Min Harden, Sarah L. Suteja, Lisda Liu, Wai Nam Tan, Wilson Wei Sheng Iyer, N. Gopalakrishna Tan, Sue Yee So, Wing Yan Yeong, Joe Poh Sheng Lim, Darren Wan-Teck Rajarethinam, Ravisankar Wong, Melissa Xin Yu |
| Author_xml | – sequence: 1 givenname: Wai Nam orcidid: 0000-0002-4323-4566 surname: Liu fullname: Liu, Wai Nam organization: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 138673, Singapore – sequence: 2 givenname: Wing Yan orcidid: 0000-0001-9647-3686 surname: So fullname: So, Wing Yan organization: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 138673, Singapore – sequence: 3 givenname: Sarah L. orcidid: 0000-0002-1029-8440 surname: Harden fullname: Harden, Sarah L. organization: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 138673, Singapore – sequence: 4 givenname: Shin Yie surname: Fong fullname: Fong, Shin Yie organization: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 138673, Singapore – sequence: 5 givenname: Melissa Xin Yu orcidid: 0000-0002-6217-5258 surname: Wong fullname: Wong, Melissa Xin Yu organization: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 138673, Singapore – sequence: 6 givenname: Wilson Wei Sheng orcidid: 0000-0003-3027-1162 surname: Tan fullname: Tan, Wilson Wei Sheng organization: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 138673, Singapore – sequence: 7 givenname: Sue Yee surname: Tan fullname: Tan, Sue Yee organization: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 138673, Singapore – sequence: 8 givenname: Jessica Kai Lin orcidid: 0000-0002-6684-6370 surname: Ong fullname: Ong, Jessica Kai Lin organization: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 138673, Singapore – sequence: 9 givenname: Ravisankar orcidid: 0000-0001-9249-7840 surname: Rajarethinam fullname: Rajarethinam, Ravisankar organization: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 138673, Singapore – sequence: 10 givenname: Min surname: Liu fullname: Liu, Min organization: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 138673, Singapore – sequence: 11 givenname: Jia Ying surname: Cheng fullname: Cheng, Jia Ying organization: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 138673, Singapore – sequence: 12 givenname: Lisda orcidid: 0000-0002-4548-2766 surname: Suteja fullname: Suteja, Lisda organization: Duke-NUS Medical School, 169857, Singapore – sequence: 13 givenname: Joe Poh Sheng orcidid: 0000-0002-6674-7153 surname: Yeong fullname: Yeong, Joe Poh Sheng organization: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 138673, Singapore – sequence: 14 givenname: N. Gopalakrishna surname: Iyer fullname: Iyer, N. Gopalakrishna organization: Duke-NUS Medical School, 169857, Singapore., Department of Head and Neck Surgery, National Cancer Centre Singapore, 169610, Singapore – sequence: 15 givenname: Darren Wan-Teck orcidid: 0000-0002-4655-0206 surname: Lim fullname: Lim, Darren Wan-Teck organization: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 138673, Singapore., Division of Medical Oncology, National Cancer Center Singapore, 169610, Singapore – sequence: 16 givenname: Qingfeng orcidid: 0000-0001-6437-1271 surname: Chen fullname: Chen, Qingfeng organization: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 138673, Singapore., Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 117593, Singapore., Singapore Immunology Network, Agency for Science, Technology and Research, 138648, Singapore |
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| Cites_doi | 10.3390/cancers12041025 10.1016/j.isci.2020.101960 10.1126/science.aar6711 10.1016/j.clcc.2018.09.007 10.1016/j.stem.2015.03.011 10.3389/fimmu.2019.01906 10.1089/scd.2012.0608 10.3389/fonc.2021.744889 10.1093/annonc/mdw217 10.4049/jimmunol.1500846 10.1016/j.celrep.2018.10.082 10.7554/eLife.54854 10.1038/s41568-021-00347-z 10.5966/sctm.2012-0084 10.1074/jbc.RA118.004549 10.1172/JCI96268 10.1016/S0140-6736(19)30956-0 10.1136/jitc-2019-000450 10.3390/cancers12082131 10.1038/s41591-018-0014-x 10.3389/fimmu.2021.644350 10.1038/s41419-021-03788-4 10.3389/fimmu.2016.00091 10.3389/fimmu.2015.00578 10.1016/j.stem.2018.06.002 10.4049/jimmunol.1000225 10.1038/nature22395 10.3390/cancers11060769 10.1002/hep.31812 10.1200/JCO.2014.59.4358 10.3389/fonc.2021.617335 10.1016/j.clinthera.2016.03.026 10.3390/cancers11101534 10.1002/cti2.1274 10.3389/fimmu.2017.00760 10.1158/1078-0432.CCR-15-2463 10.3389/fimmu.2019.02298 10.1038/cmi.2012.17 10.1136/jitc-2020-001460 10.1038/s41467-021-21795-z 10.1038/s41434-021-00246-w 10.1136/jitc-2020-002128 10.1016/j.jim.2004.10.008 10.3332/ecancer.2019.961 10.3389/fimmu.2016.00504 10.1136/gutjnl-2017-315201 10.1016/j.cyto.2018.02.012 10.1016/j.jhep.2016.05.032 10.1016/j.annonc.2020.10.478 10.3389/fimmu.2019.02873 10.1038/s41590-019-0511-1 10.1016/j.blre.2018.11.002 10.3390/jcm8122168 10.1038/s41571-019-0218-0 10.1007/978-1-0716-0759-6_14 10.1038/ni1582 10.3389/fimmu.2020.00784 10.1089/10430349950018030 10.1016/j.jcyt.2020.12.002 10.1038/s41422-020-0343-4 |
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| References | e_1_3_2_26_2 e_1_3_2_49_2 e_1_3_2_28_2 e_1_3_2_41_2 e_1_3_2_20_2 e_1_3_2_43_2 e_1_3_2_62_2 e_1_3_2_22_2 e_1_3_2_45_2 e_1_3_2_24_2 e_1_3_2_47_2 e_1_3_2_60_2 e_1_3_2_9_2 e_1_3_2_16_2 e_1_3_2_37_2 e_1_3_2_7_2 e_1_3_2_18_2 e_1_3_2_39_2 e_1_3_2_54_2 e_1_3_2_10_2 e_1_3_2_31_2 e_1_3_2_52_2 e_1_3_2_5_2 e_1_3_2_12_2 e_1_3_2_33_2 e_1_3_2_58_2 e_1_3_2_3_2 e_1_3_2_14_2 e_1_3_2_35_2 e_1_3_2_56_2 e_1_3_2_27_2 e_1_3_2_48_2 e_1_3_2_29_2 e_1_3_2_40_2 e_1_3_2_21_2 e_1_3_2_42_2 Gong J. H. (e_1_3_2_50_2) 1994; 8 e_1_3_2_23_2 e_1_3_2_44_2 e_1_3_2_25_2 e_1_3_2_46_2 e_1_3_2_61_2 e_1_3_2_15_2 e_1_3_2_38_2 e_1_3_2_8_2 e_1_3_2_17_2 e_1_3_2_59_2 e_1_3_2_6_2 e_1_3_2_19_2 e_1_3_2_30_2 e_1_3_2_53_2 e_1_3_2_32_2 e_1_3_2_51_2 e_1_3_2_11_2 e_1_3_2_34_2 e_1_3_2_57_2 e_1_3_2_4_2 e_1_3_2_13_2 e_1_3_2_36_2 e_1_3_2_55_2 e_1_3_2_2_2 |
| References_xml | – ident: e_1_3_2_23_2 doi: 10.3390/cancers12041025 – ident: e_1_3_2_41_2 doi: 10.1016/j.isci.2020.101960 – ident: e_1_3_2_8_2 doi: 10.1126/science.aar6711 – volume: 8 start-page: 652 year: 1994 ident: e_1_3_2_50_2 article-title: Characterization of a human cell line (Nk-92) with phenotypical and functional characteristics of activated natural killer cells publication-title: Leukemia – ident: e_1_3_2_33_2 doi: 10.1016/j.clcc.2018.09.007 – ident: e_1_3_2_10_2 doi: 10.1016/j.stem.2015.03.011 – ident: e_1_3_2_55_2 doi: 10.3389/fimmu.2019.01906 – ident: e_1_3_2_17_2 doi: 10.1089/scd.2012.0608 – ident: e_1_3_2_32_2 doi: 10.3389/fonc.2021.744889 – ident: e_1_3_2_35_2 doi: 10.1093/annonc/mdw217 – ident: e_1_3_2_14_2 doi: 10.4049/jimmunol.1500846 – ident: e_1_3_2_30_2 doi: 10.1016/j.celrep.2018.10.082 – ident: e_1_3_2_48_2 doi: 10.7554/eLife.54854 – ident: e_1_3_2_45_2 doi: 10.1038/s41568-021-00347-z – ident: e_1_3_2_39_2 doi: 10.5966/sctm.2012-0084 – ident: e_1_3_2_36_2 doi: 10.1074/jbc.RA118.004549 – ident: e_1_3_2_58_2 doi: 10.1172/JCI96268 – ident: e_1_3_2_24_2 doi: 10.1016/S0140-6736(19)30956-0 – ident: e_1_3_2_47_2 doi: 10.1136/jitc-2019-000450 – ident: e_1_3_2_20_2 doi: 10.3390/cancers12082131 – ident: e_1_3_2_21_2 doi: 10.1038/s41591-018-0014-x – ident: e_1_3_2_25_2 doi: 10.3389/fimmu.2021.644350 – ident: e_1_3_2_28_2 doi: 10.1038/s41419-021-03788-4 – ident: e_1_3_2_37_2 doi: 10.3389/fimmu.2016.00091 – ident: e_1_3_2_15_2 doi: 10.3389/fimmu.2015.00578 – ident: e_1_3_2_18_2 doi: 10.1016/j.stem.2018.06.002 – ident: e_1_3_2_27_2 doi: 10.4049/jimmunol.1000225 – ident: e_1_3_2_7_2 doi: 10.1038/nature22395 – ident: e_1_3_2_16_2 doi: 10.3390/cancers11060769 – ident: e_1_3_2_42_2 doi: 10.1002/hep.31812 – ident: e_1_3_2_59_2 doi: 10.1200/JCO.2014.59.4358 – ident: e_1_3_2_5_2 doi: 10.3389/fonc.2021.617335 – ident: e_1_3_2_3_2 doi: 10.1016/j.clinthera.2016.03.026 – ident: e_1_3_2_54_2 doi: 10.3390/cancers11101534 – ident: e_1_3_2_56_2 doi: 10.1002/cti2.1274 – ident: e_1_3_2_19_2 doi: 10.3389/fimmu.2017.00760 – ident: e_1_3_2_29_2 doi: 10.1158/1078-0432.CCR-15-2463 – ident: e_1_3_2_46_2 doi: 10.3389/fimmu.2019.02298 – ident: e_1_3_2_40_2 doi: 10.1038/cmi.2012.17 – ident: e_1_3_2_4_2 doi: 10.1136/jitc-2020-001460 – ident: e_1_3_2_44_2 doi: 10.1038/s41467-021-21795-z – ident: e_1_3_2_9_2 doi: 10.1038/s41434-021-00246-w – ident: e_1_3_2_49_2 doi: 10.1136/jitc-2020-002128 – ident: e_1_3_2_51_2 doi: 10.1016/j.jim.2004.10.008 – ident: e_1_3_2_2_2 doi: 10.3332/ecancer.2019.961 – ident: e_1_3_2_38_2 doi: 10.3389/fimmu.2016.00504 – ident: e_1_3_2_43_2 doi: 10.1136/gutjnl-2017-315201 – ident: e_1_3_2_31_2 doi: 10.1016/j.cyto.2018.02.012 – ident: e_1_3_2_26_2 doi: 10.1016/j.jhep.2016.05.032 – ident: e_1_3_2_12_2 doi: 10.1016/j.annonc.2020.10.478 – ident: e_1_3_2_52_2 doi: 10.3389/fimmu.2019.02873 – ident: e_1_3_2_57_2 doi: 10.1038/s41590-019-0511-1 – ident: e_1_3_2_11_2 doi: 10.1016/j.blre.2018.11.002 – ident: e_1_3_2_34_2 doi: 10.3390/jcm8122168 – ident: e_1_3_2_6_2 doi: 10.1038/s41571-019-0218-0 – ident: e_1_3_2_60_2 doi: 10.1007/978-1-0716-0759-6_14 – ident: e_1_3_2_13_2 doi: 10.1038/ni1582 – ident: e_1_3_2_22_2 doi: 10.3389/fimmu.2020.00784 – ident: e_1_3_2_62_2 doi: 10.1089/10430349950018030 – ident: e_1_3_2_53_2 doi: 10.1016/j.jcyt.2020.12.002 – ident: e_1_3_2_61_2 doi: 10.1038/s41422-020-0343-4 |
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| Snippet | In recent decades, chimeric antigen receptor (CAR)–engineered immune effector cells have demonstrated promising antileukemic activity. Nevertheless, their... In recent decades, chimeric antigen receptor (CAR)-engineered immune effector cells have demonstrated promising antileukemic activity. Nevertheless, their... |
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| SubjectTerms | Animals B7-H1 Antigen - metabolism Biomedicine and Life Sciences Cancer Disease Models, Animal Killer Cells, Natural Ligands Mice Neoplasms - metabolism Nivolumab - pharmacology Programmed Cell Death 1 Receptor Receptors, Chimeric Antigen - metabolism SciAdv r-articles Tumor Microenvironment |
| Title | Successful targeting of PD-1/PD-L1 with chimeric antigen receptor-natural killer cells and nivolumab in a humanized mouse cancer model |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/36417514 https://www.proquest.com/docview/2739741387 https://pubmed.ncbi.nlm.nih.gov/PMC9683725 |
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