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

National Institutes of Health, National Cancer Institute, Surgery Branch, Bethesda, MD 20892-1201, USA.
Journal of Clinical Oncology (Impact Factor: 18.43). 02/2011; 29(7):917-24. DOI: 10.1200/JCO.2010.32.2537
Source: PubMed


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.

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Available from: Chyi-Chia Richard Lee
    • "Adoptive cellular therapy in which autologous tumour infiltrating lymphocytes (TILs) are harvested from human melanoma patients, expanded ex vivo and then re-infused intravenously postlymphodepletion has also resulted in some incredible effects in clinical trials with advanced stage melanoma patients (Rosenberg and Dudley, 2009). Engineering of autologous T-cells ex vivo to alter the T-cell receptor (TCR) has also been performed enabling T-cells to engage with tumour cells in patients where the unaltered autologous cells might be unable to bind to the appropriate targets (Robbins et al., 2011). Latterly T-cells with chimeric antigen receptors (CAR T-cells) have also been developed in pre-clinical melanoma models to enhance T-cell target recognition and killing (Zhang et al., 2014). "
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