Journal
NATURE BIOTECHNOLOGY
Volume 36, Issue 4, Pages 346-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nbt.4086
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Funding
- Project for Development of Innovative Research on Cancer Therapeutics (P-DIRECT) [14532963]
- Practical Research for Innovative Cancer Control
- Project for Cancer Research and Therapeutic Evolution (P-CREATE) [16770206]
- Japan Agency for Medical Research and Development (AMED)
- Noile-Immune Biotech Inc.
- Grants-in-Aid for Scientific Research [16H02474] Funding Source: KAKEN
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Infiltration, accumulation, and survival of chimeric antigen receptor T (CAR-T) cells in solid tumors is crucial for tumor clearance. We engineered CAR-T cells to express interleukin (IL)-7 and CCL19 (7 x 19 CAR-T cells), as these factors are essential for the maintenance of T-cell zones in lymphoid organs. In mice, 7 x 19 CAR-T cells achieved complete regression of pre-established solid tumors and prolonged mouse survival, with superior anti-tumor activity compared to conventional CAR-T cells. Histopathological analyses showed increased infiltration of dendritic cells (DC) and T cells into tumor tissues following 7 x 19 CAR-T cell therapy. Depletion of recipient T cells before 7 x 19 CAR-T cell administration dampened the therapeutic effects of 7 x 19 CAR-T cell treatment, suggesting that CAR-T cells and recipient immune cells collaborated to exert anti-tumor activity. Following treatment of mice with 7 x 19 CAR-T cells, both recipient conventional T cells and administered CAR-T cells generated memory responses against tumors.
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