Tumor Regression in Patients With Metastatic Synovial Cell Sarcoma and Melanoma Using Genetically Engineered Lymphocytes Reactive With NY-ESO-1

TLDR

Adoptive immunotherapy with tumor‑infiltrating lymphocytes is an effective treatment for metastatic melanoma, and the NY‑ESO‑1 antigen, expressed in most synovial cell sarcoma and a subset of melanoma and epithelial tumors, is a promising immune‑therapy target. The trial aimed to assess whether autologous T cells engineered with an NY‑ESO‑1‑specific TCR could induce tumor regression in metastatic melanoma and synovial cell sarcoma. Patients received preparative chemotherapy followed by infusion of autologous TCR‑engineered T cells plus IL‑2, and responses were assessed by RECIST criteria. The therapy produced objective responses in 4 of 6 synovial cell sarcoma patients and 5 of 11 melanoma patients, including two durable complete regressions in melanoma and an 18‑month partial response in synovial cell sarcoma, demonstrating the efficacy of NY‑ESO‑1‑targeted TCR gene therapy and marking the first successful treatment of a non‑melanoma tumor with this approach.

Abstract

Adoptive immunotherapy using tumor-infiltrating lymphocytes represents an effective cancer treatment for patients with metastatic melanoma. The NY-ESO-1 cancer/testis antigen, which is expressed in 80% of patients with synovial cell sarcoma and approximately 25% of patients with melanoma and common epithelial tumors, represents an attractive target for immune-based therapies. The current trial was carried out to evaluate the ability of adoptively transferred autologous T cells transduced with a T-cell receptor (TCR) directed against NY-ESO-1 to mediate tumor regression in patients with metastatic melanoma and synovial cell sarcoma.A clinical trial was performed in patients with metastatic melanoma or metastatic synovial cell sarcoma refractory to all standard treatments. Patients with NY-ESO-1-positive tumors were treated with autologous TCR-transduced T cells plus 720,000 iU/kg of interleukin-2 to tolerance after preparative chemotherapy. Objective clinical responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST).Objective clinical responses were observed in four of six patients with synovial cell sarcoma and five of 11 patients with melanoma bearing tumors expressing NY-ESO-1. Two of 11 patients with melanoma demonstrated complete regressions that persisted after 1 year. A partial response lasting 18 months was observed in one patient with synovial cell sarcoma.These observations indicate that TCR-based gene therapies directed against NY-ESO-1 represent a new and effective therapeutic approach for patients with melanoma and synovial cell sarcoma. To our knowledge, this represents the first demonstration of the successful treatment of a nonmelanoma tumor using TCR-transduced T cells.