Tethered IL-15 augments antitumor activity and promotes a stem-cell memory subset in tumor-specific T cells

Proceedings of the National Academy of Sciences of the United States of America - Tập 113 Số 48 - 2016
Lenka V. Hurton1,2, Harjeet Singh3, Amer Najjar4, Kirsten C. Switzer3, Tiejuan Mi3, Sourindra N. Maiti3, Simon Olivares3, Brian Rabinovich3, Helen Huls5,6, Marie-Andrée Forget3,7, Vrushali Datar4, Partow Kebriaei8, Dean A. Lee3, Richard E. Champlin8, Laurence J.N. Cooper9,10
1Division of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;; The University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030;
2The University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030;
3Division of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
4Cancer Systems Imaging, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
5Division of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;; Intrexon, Germantown, MD 20876;
6Intrexon, Germantown, MD 20876;
7Melanoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
8Stem Cell Transplantation and Cellular Therapy, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
9Division of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;; ZIOPHARM Oncology, Inc., Boston, MA 02129
10ZIOPHARM Oncology, Inc., Boston, MA 02129

Tóm tắt

Significance We describe an approach based on cytokine therapeutics to enhance the persistence and effectiveness of T-cell–based immunotherapies using chimeric antigen receptors (CARs). This strategy is effective without the use of high-dose exogenous cytokines that are typically associated with toxicities. Moreover, we report that the persistence of the least differentiated memory T cell, the T-memory stem cell, was promoted by signaling induced by a membrane-bound chimeric IL-15 cytokine-fusion molecule. These findings may contribute to improving the safety and therapeutic efficacy of CAR-based immunotherapies of patients with advanced cancer.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 113 Số 48

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