期刊
NATURE COMMUNICATIONS
卷 13, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-30860-0
关键词
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资金
- Alex's Lemonade Stand Foundation/Northwestern Mutual Young Investigator Award
- Washington University SPORE in Leukemia Developmental Research Award
- Washington University Division of Physician-Scientists - Burroughs Wellcome Fund Physician-Scientist Institutional Award
- NCI Research Specialist Award [R50 CA211466]
- International Myeloma Society
- Paula and Roger Riney Foundation Translational Research Grant
- NCI Outstanding Investigator Award [R35 CA210084]
- NIH [P50 CA171963]
- Children's Discovery Institute Award
A study has found that a long-acting form of recombinant human interleukin-7 can enhance the efficacy of chimeric antigen receptor (CAR) T cell therapy, promoting cell proliferation, persistence, and cytotoxicity, resulting in long-term tumor-free survival.
Chimeric antigen receptor (CAR) T cell therapy is routinely used to treat patients with refractory hematologic malignancies. However, a significant proportion of patients experience suboptimal CAR T cell cytotoxicity and persistence that can permit tumor cell escape and disease relapse. Here we show that a prototype pro-lymphoid growth factor is able to enhance CAR T cell efficacy. We demonstrate that a long-acting form of recombinant human interleukin-7 (IL-7) fused with hybrid Fc (rhIL-7-hyFc) promotes proliferation, persistence and cytotoxicity of human CAR T cells in xenogeneic mouse models, and murine CAR T cells in syngeneic mouse models, resulting in long-term tumor-free survival. Thus, rhIL-7-hyFc represents a tunable clinic-ready adjuvant for improving suboptimal CAR T cell activity. Chimeric antigen receptor T cells represent a breakthrough treatment in hematologic malignancies, but insufficient level of cytotoxicity and persistence of T cells might compromise success. Authors show here that a recombinant long acting form of interleukin-7 enhances proliferation, persistence and cytotoxicity of the engineered T cells, resulting in long term disease remission.
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