Inicio / Oncología / Abstracts de oncología / Immunogenic Chemotherapy…

Immunogenic Chemotherapy Enhances Recruitment of CAR-T Cells to Lung Tumors and Improves Antitumor Efficacy when Combined with Checkpoint Blockade

0 / 5 (0 votos)
Immunogenic Chemotherapy Enhances Recruitment of CAR-T Cells to Lung Tumors and Improves Antitumor Efficacy when Combined with Checkpoint Blockade

Cancer Cell

Fecha de publicación: 24 de diciembre de 2020

DOI: https://doi.org/10.1016/j.ccell.2020.11.005

Autores: Shivani Srivastava, Scott N. Furlan, Carla A. Jaeger-Ruckstuhl, Megha Sarvothama, Carolina Berger, Kimberly S. Smythe, Sarah M. Garrison, Jennifer M. Specht, Sylvia M. Lee, Robert A. Amezquita, Valentin Voillet, Vishaka Muhunthan, Sushma Yechan-Gunja, Smitha P.S. Pillai, Christoph Rader, A. McGarry Houghton, Robert H. Pierce, Raphael Gottardo, David G. Maloney,Stanley R. Riddell

Background: Adoptive therapy using chimeric antigen receptor-modified T cells (CAR-T cells) is effective in hematologic but not epithelial malignancies, which cause the greatest mortality. In breast and lung cancer patients, CAR-T cells targeting the tumor-associated antigen receptor tyrosine kinase-like orphan receptor 1 (ROR1) infiltrate tumors poorly and become dysfunctional. To test strategies for enhancing efficacy, we adapted the KrasLSL-G12D/+;p53f/f autochthonous model of lung adenocarcinoma to express the CAR target ROR1. Murine ROR1 CAR-T cells transferred after lymphodepletion with cyclophosphamide (Cy) transiently control tumor growth but infiltrate tumors poorly and lose function, similar to what is seen in patients. Adding oxaliplatin (Ox) to the lymphodepletion regimen activates tumor macrophages to express T-cell-recruiting chemokines, resulting in improved CAR-T cell infiltration, remodeling of the tumor microenvironment, and increased tumor sensitivity to anti-PD-L1. Combination therapy with Ox/Cy and anti-PD-L1 synergistically improves CAR-T cell-mediated tumor control and survival, providing a strategy to improve CAR-T cell efficacy in the clinic.

Leer más

Comentarios

Para dejar un comentario antes debes iniciar sesión:

¿No tienes una cuenta?

Regístrate a través de éste enlace.