期刊
JCI INSIGHT
卷 2, 期 5, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.90772
关键词
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资金
- Hollings Cell Evaluation Therapy
- Hollings Cell Evaluation & Therapy, and Hollings Biostatistics Shared Resources, Hollings Cancer Center, MUSC [P30 CA138313]
- NIH [F30 CA200272, T32 GM008716, F31 CA192787]
- Jeane B. Kempner Foundation
- ACS [122704-PF-13-084-01-LIB]
- NCI [R01 CA175061, R01 CA208514]
- KL2 South Carolina Clinical & Translational Research grant [UL1 TR000062]
- ACS-IRG grant [016623-004]
- MUSC start-up funds
Adoptive immunotherapy for solid tumors relies on infusing large numbers of T cells to mediate successful antitumor responses in patients. While long-term rapid-expansion protocols (REPs) produce sufficient numbers of CD8(+) T cells for treatment, they also cause decline in the cell's therapeutic fitness. In contrast, we discovered that IL-17-producing CD4(+) T cells (Th17 cells) do not require REPs to expand 5,000-fold over 3 weeks. Also, unlike Th1 cells, Th17 cells do not exhibit hallmarks of senescence or apoptosis, retaining robust antitumor efficacy in vivo. Three-week-expanded Th17 cells eliminated melanoma as effectively as Th17 cells expanded for 1 week when infused in equal numbers into mice. However, treating mice with large recalcitrant tumors required the infusion of all cells generated after 2 or 3 weeks of expansion, while the cell yield obtained after 1-week expansion was insufficient. Long-term-expanded Th17 cells also protected mice from tumor rechallenge including lung metastasis. Importantly, 2-week-expanded human chimeric antigen receptor-positive (CAR(+)) Th17 cells also retained their ability to regress human mesothelioma, while CAR(+) Th1 cells did not. Our results indicate that tumor-reactive Th17 cells are an effective cell therapy for cancer, remaining uncompromised when expanded for a long duration owing to their resistance to senescence.
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