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posted on 2023-12-07, 17:00 authored by Theodore S. Nowicki, Cole W. Peters, Crystal Quiros, Conner K. Kidd, Moe Kawakami, Alexandra M. Klomhaus, Ignacio Baselga-Carretero, Paula Kaplan-Lefko, Mignonette H. Macabali, Ivan Perez Garcilazo, Beata Berent-Maoz, Begoña Comin-Anduix, Antoni Ribas Association of CD4 Th2 cytokine polyfunctionality with lower peak TCR+ T-cell proportion in peripheral circulation in vivo following adoptive cell transfer. CD4 Th2 PSI score is weakly associated with lower peak values of TCR+% T-cell populations following infusion of TCR-T cell products (Pearson’s r).
Funding
National Cancer Institute (NCI)
United States Department of Health and Human Services
Find out more...California Institute for Regenerative Medicine (CIRM)
Hyundai Hope On Wheels (Hope On Wheels)
Ruby Family Foundation
Parker Institute for Cancer Immunotherapy (Parker Institute)
Ressler Family Fund
Ken and Donna Schultz
Todd and Donna Jones
Thomas Stutz
History
ARTICLE ABSTRACT
Transgenic T-cell receptor (TCR) T cell–based adoptive cell therapies for solid tumors are associated with dramatic initial response rates, but there remain many instances of treatment failure and disease relapse. The association of infusion product cytokine profiles with clinical response has not been explored in the context of TCR T-cell therapy products. Single-cell antigen-dependent secretomic and proteomic analysis of preinfusion clinical TCR T-cell therapy products revealed that TNFα cytokine functionality of CD8+ T cells and phospho-STAT3 signaling in these cells were both associated with superior clinical responsiveness to therapy. By contrast, CD4+ T-helper 2 cell cytokine profiles were associated with inferior clinical responses. In parallel, preinfusion levels of IL15, Flt3-L, and CX3CL1 were all found to be associated with clinical response to therapy. These results have implications for the development of therapeutic biomarkers and identify potential targets for enrichment in the design of transgenic TCR T-cell therapies for solid tumors.
