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. Tine, Stephan A. Grupp, Gregg D. Fine and Ioanna Eleftheriadou ()
Additional contact information
Alexandra Gyurdieva: GlaxoSmithKline
Stefan Zajic: GlaxoSmithKline
Ya-Fang Chang: GlaxoSmithKline
E. Andres Houseman: GlaxoSmithKline
Shan Zhong: GlaxoSmithKline
Jaegil Kim: GlaxoSmithKline
Michael Nathenson: GlaxoSmithKline
Thomas Faitg: GlaxoSmithKline
Mary Woessner: GlaxoSmithKline
David C. Turner: GlaxoSmithKline
Aisha N. Hasan: GlaxoSmithKline
John Glod: National Cancer Institute
Rosandra N. Kaplan: National Cancer Institute
Sandra P. D’Angelo: Memorial Sloan Kettering Cancer Center
Dejka M. Araujo: University of Texas/MD Anderson Cancer Center
Warren A. Chow: City of Hope Comprehensive Cancer Center
Mihaela Druta: H. Lee Moffitt Cancer Center
George D. Demetri: Dana-Farber Cancer Institute and Ludwig Center at Harvard
Brian A. Tine: Washington University in St. Louis School of Medicine
Stephan A. Grupp: Children’s Hospital of Philadelphia and University of Pennsylvania
Gregg D. Fine: GlaxoSmithKline
Ioanna Eleftheriadou: GlaxoSmithKline

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: 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

Date: 2022
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DOI: 10.1038/s41467-022-32491-x

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