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Published on: June 13, 2019
Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered
Paul F Robbins1, Richard A Morgan, Steven A Feldman
1National Institutes of Health, National Cancer Institute, Surgery Branch, Bethesda, MD 20892-1201, USA. Paul_Robbins@nih.gov
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.
Insights
Adoptive immunotherapy using T-cell receptor (TCR) gene therapy targeting NY-ESO-1 showed significant tumor regression in patients with metastatic melanoma and synovial cell sarcoma. This approach offers a novel and effective treatment strategy for these challenging cancers.
Area of Science:
- Oncology
- Immunotherapy
- Gene Therapy
Background:
- Adoptive immunotherapy with tumor-infiltrating lymphocytes is effective for metastatic melanoma.
- The NY-ESO-1 antigen is expressed in synovial cell sarcoma (80%) and melanoma (25%), making it a viable target for immunotherapy.
Purpose of the Study:
- To evaluate the efficacy of adoptively transferred autologous T cells genetically engineered with a T-cell receptor (TCR) against NY-ESO-1.
- To assess tumor regression in patients with metastatic melanoma and synovial cell sarcoma.
Main Methods:
- A clinical trial was conducted on patients with metastatic melanoma or synovial cell sarcoma resistant to standard treatments.
- Patients received autologous TCR-transduced T cells targeting NY-ESO-1, along with interleukin-2, after preparative chemotherapy.
- Tumor response was measured using Response Evaluation Criteria in Solid Tumors (RECIST).
Main Results:
- Objective clinical responses were observed in 4/6 patients with synovial cell sarcoma and 5/11 patients with melanoma.
- Complete regressions lasting over a year were seen in 2/11 melanoma patients.
- One synovial cell sarcoma patient achieved a partial response lasting 18 months.
Conclusions:
- TCR-based gene therapy targeting NY-ESO-1 is a promising new therapeutic strategy for melanoma and synovial cell sarcoma.
- This study marks the first successful use of TCR-transduced T cells for treating a non-melanoma tumor.
