Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1 - PubMed (original) (raw)
Clinical Trial
. 2011 Mar 1;29(7):917-24.
doi: 10.1200/JCO.2010.32.2537. Epub 2011 Jan 31.
Richard A Morgan, Steven A Feldman, James C Yang, Richard M Sherry, Mark E Dudley, John R Wunderlich, Azam V Nahvi, Lee J Helman, Crystal L Mackall, Udai S Kammula, Marybeth S Hughes, Nicholas P Restifo, Mark Raffeld, Chyi-Chia Richard Lee, Catherine L Levy, Yong F Li, Mona El-Gamil, Susan L Schwarz, Carolyn Laurencot, Steven A Rosenberg
Affiliations
- PMID: 21282551
- PMCID: PMC3068063
- DOI: 10.1200/JCO.2010.32.2537
Clinical Trial
Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1
Paul F Robbins et al. J Clin Oncol. 2011.
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.
Conflict of interest statement
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
Figures
Fig 1.
Computed tomography scans demonstrating tumor regression. Radiologic studies were obtained before therapy and after adoptive transfer of NY-ESO-1 T-cell receptor (TCR) –transduced T cells. Tumors indicated by arrows. (A) Regression of multiple recurrent axillary lymph nodes from metastatic melanoma in patient 5 with a complete response now ongoing at 20 months. (B) Regression of a perihepatic chest wall lesion of synovial cell sarcoma in patient 16, who demonstrated a partial response lasting 8 months. (C) Regression of multiple lung metastases of synovial cell sarcoma in patient 13, who received two treatments with NY-ESO-1 TCR-transduced T cells and demonstrated a partial response lasting 18 months. No toxicities attributable to the administered cells were observed in these patients.
Fig 1.
Computed tomography scans demonstrating tumor regression. Radiologic studies were obtained before therapy and after adoptive transfer of NY-ESO-1 T-cell receptor (TCR) –transduced T cells. Tumors indicated by arrows. (A) Regression of multiple recurrent axillary lymph nodes from metastatic melanoma in patient 5 with a complete response now ongoing at 20 months. (B) Regression of a perihepatic chest wall lesion of synovial cell sarcoma in patient 16, who demonstrated a partial response lasting 8 months. (C) Regression of multiple lung metastases of synovial cell sarcoma in patient 13, who received two treatments with NY-ESO-1 TCR-transduced T cells and demonstrated a partial response lasting 18 months. No toxicities attributable to the administered cells were observed in these patients.
Fig 2.
Serum anti–NY-ESO-1 antibody titers. The titers of anti–NY-ESO-1 antibodies in pretreatment sera were evaluated by enzyme-linked immunosorbent assay. Clinically responding patients are designated with square symbols, and nonresponding patients are designated with diamonds. Clinical responses were not correlated positively or negatively with anti–NY-ESO-1 antibody titers.
Fig 3.
Correlations between T-cell persistence and enzyme-linked immunosorbent spot (ELISPOT) responses. Highly significant correlations were found (A) between NY-ESO-1 tetramer and Vβ13.1 expression (_r_2 = 0.82; P < .001), (B) between NY-ESO-1 peptide–reactive interferon gamma (IFN-γ) ELISPOTs and NY-ESO-1 tetramer expression (_r_2 = 0.72; P < .001), and (C) between NY-ESO-1 peptide–reactive ELISPOTs and Vβ13.1 expression (_r_2 = 0.70; P < .001) in patient peripheral-blood mononuclear cells (PBMCs) obtained approximately 1 month after adoptive transfer.
Fig A1.
Titration of response to NY-ESO-1 peptide. Soluble interferon gamma (IFN-γ) levels were measured in overnight cocultures of 105 cells from samples of infused transduced T cells from patients with (A) melanoma and (B) synovial cell sarcoma with 105 T2 cells that had been pulsed with the NY-ESO-1:157-165 peptide. Responses to the negative control gp100:154-162 peptide were all less than 100 pg/mL of IFN-γ.
Comment in
- Immunotherapy: gene therapy for soft-tissue tumors.
Richards L. Richards L. Nat Rev Clin Oncol. 2011 Mar 1;8(4):192. doi: 10.1038/nrclinonc.2011.26. Nat Rev Clin Oncol. 2011. PMID: 21451490 No abstract available. - Adoptive T-cell therapy of melanoma using designer T-cell receptors.
Margolin K. Margolin K. Curr Oncol Rep. 2011 Dec;13(6):427-9. doi: 10.1007/s11912-011-0196-6. Curr Oncol Rep. 2011. PMID: 21931938 No abstract available.
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