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

Lenka V. Hurton(The University of Texas MD Anderson Cancer Center), Harjeet Singh(The University of Texas MD Anderson Cancer Center), Amer Najjar(The University of Texas MD Anderson Cancer Center), Kirsten C. Switzer(The University of Texas MD Anderson Cancer Center), Tiejuan Mi(The University of Texas MD Anderson Cancer Center), Sourindra N. Maiti(The University of Texas MD Anderson Cancer Center), Simon Olivares(The University of Texas MD Anderson Cancer Center), Brian Rabinovich(The University of Texas MD Anderson Cancer Center), Helen Huls(The University of Texas MD Anderson Cancer Center), Marie-Andrée Forget(The University of Texas MD Anderson Cancer Center), Vrushali Datar(The University of Texas MD Anderson Cancer Center), Partow Kebriaei(The University of Texas MD Anderson Cancer Center), Dean A. Lee(The University of Texas MD Anderson Cancer Center), Richard E. Champlin(The University of Texas MD Anderson Cancer Center), Laurence J.N. Cooper(The University of Texas MD Anderson Cancer Center)
Proceedings of the National Academy of Sciences
November 14, 2016
Cited by 452Open Access
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Abstract

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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