학술논문

Biomarker correlates with response to NY-ESO-1 TCR T cells in patients with synovial sarcoma
Document Type
article
Source
Nature Communications. 13(1)
Subject
Biomedical and Clinical Sciences
Oncology and Carcinogenesis
Immunology
Cancer
Clinical Research
Development of treatments and therapeutic interventions
5.2 Cellular and gene therapies
Antigens
Neoplasm
Biomarkers
CD8-Positive T-Lymphocytes
Humans
Membrane Proteins
Receptors
Antigen
T-Cell
Sarcoma
Synovial
Tumor Microenvironment
Language
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