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

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.

• Authors: 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 Grupp, Gregg D Fine, Ioanna Eleftheriadou
• Journal: Nature communications (Nat Commun) Vol. 13 Issue 1 Pg. 5296 (09 08 2022) ISSN: 2041-1723 [Electronic] England
• PMID: 36075914 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

Chemical References

• Antigens, Neoplasm
• Biomarkers
• Membrane Proteins
• Receptors, Antigen, T-Cell

Topics

• Antigens, Neoplasm (metabolism)
• Biomarkers (metabolism)
• CD8-Positive T-Lymphocytes (metabolism)
• Humans
• Membrane Proteins (genetics, metabolism)
• Receptors, Antigen, T-Cell (genetics, metabolism)
• Sarcoma, Synovial (genetics, pathology, therapy)
• Tumor Microenvironment