Biomarker correlates with response to NY-ESO-1 TCR T cells in patients with synovial sarcoma

Alexandra Gyurdieva, Stefan Zajic, Ya Fang Chang, E. Andres Houseman, Shan Zhong, Jaegil Kim, Michael Nathenson, Thomas Faitg, Mary Woessner, David C. Turner, Aisha N. Hasan, John Glod, Rosandra N. Kaplan, Sandra P. D’Angelo, Dejka M. Araujo, Warren A. Chow, Mihaela Druta, George D. Demetri, Brian A. Van Tine, Stephan A. GruppGregg D. Fine, Ioanna Eleftheriadou

Research output: Contribution to journalArticlepeer-review

Abstract

Autologous T cells transduced to express a high affinity T-cell receptor specific to NY-ESO-1 (letetresgene autoleucel, lete-cel) show promise in the treatment of metastatic synovial sarcoma, with 50% overall response rate. The efficacy of lete-cel treatment in 45 synovial sarcoma patients (NCT01343043) has been previously reported, however, biomarkers predictive of response and resistance remain to be better defined. This post-hoc analysis identifies associations of response to lete-cel with lymphodepleting chemotherapy regimen (LDR), product attributes, cell expansion, cytokines, and tumor gene expression. Responders have higher IL-15 levels pre-infusion (p = 0.011) and receive a higher number of transduced effector memory (CD45RA- CCR7-) CD8 + cells per kg (p = 0.039). Post-infusion, responders have increased IFNγ, IL-6, and peak cell expansion (p < 0.01, p < 0.01, and p = 0.016, respectively). Analysis of tumor samples post-treatment illustrates lete-cel infiltration and a decrease in expression of macrophage genes, suggesting remodeling of the tumor microenvironment. Here we report potential predictive and pharmacodynamic markers of lete-cel response that may inform LDR, cell dose, and strategies to enhance anticancer efficacy.

Original languageEnglish
Article number5296
JournalNature communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

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