Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1

J Clin Oncol. 2011 Mar 1;29(7):917-24. doi: 10.1200/JCO.2010.32.2537. Epub 2011 Jan 31.

Abstract

Purpose: 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.

Patients and methods: 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).

Results: 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.

Conclusion: 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.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / immunology
  • Epigenesis, Genetic
  • Female
  • Genetic Engineering
  • Humans
  • Immunotherapy / methods*
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Male
  • Melanoma / immunology
  • Melanoma / mortality
  • Melanoma / secondary
  • Melanoma / therapy*
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • Risk Assessment
  • Sarcoma, Synovial / immunology
  • Sarcoma, Synovial / mortality
  • Sarcoma, Synovial / secondary
  • Sarcoma, Synovial / therapy*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology
  • Skin Neoplasms / therapy*
  • Survival Analysis
  • Treatment Outcome
  • Young Adult

Substances

  • Cancer Vaccines