0

IL-7 and CCL19 Expression in CAR-T Cells Improves Immune Cell Infiltration and CAR-T Cell Survival in the Tumor

Keishi Adachi, Yosuke Kano, Tomohiko Nagai, Namiko Okuyama, Yukimi Sakoda, Koji Tamada

Nat Biotechnol. 2018 Apr;36(4):346-351.

PMID: 29505028

Abstract:

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 × 19 CAR-T cells), as these factors are essential for the maintenance of T-cell zones in lymphoid organs. In mice, 7 × 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 × 19 CAR-T cell therapy. Depletion of recipient T cells before 7 × 19 CAR-T cell administration dampened the therapeutic effects of 7 × 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 × 19 CAR-T cells, both recipient conventional T cells and administered CAR-T cells generated memory responses against tumors.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
IAR42413129 MIP-3beta from mouse MIP-3beta from mouse Price
IAR4248609 Interleukin-7 from mouse Interleukin-7 from mouse Price
qrcode