Tethered IL-15 augments antitumor activity and promotes a stem-cell memory subset in tumor-specific T cells
Lenka V. HurtonDivision of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;Harjeet SinghDivision of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;Amer NajjarCancer Systems Imaging, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;Kirsten C. SwitzerDivision of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;Tiejuan MiDivision of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;Sourindra N. MaitiDivision of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;Simon OlivaresDivision of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;Brian RabinovichDivision of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;Helen HulsDivision of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;Marie-Andrée ForgetDivision of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;Vrushali DatarCancer Systems Imaging, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;Partow KebriaeiStem Cell Transplantation and Cellular Therapy, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;Dean A. LeeDivision of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;Richard E. ChamplinStem Cell Transplantation and Cellular Therapy, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;Laurence J.N. CooperDivision of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;
2016en
ABI
Аннотация
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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