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

Paul F. Robbins, 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 & 1 others Steven A. Rosenberg

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)917-924
Number of pages8
JournalJournal of Clinical Oncology
Volume29
Issue number7
DOIs
StatePublished - Mar 1 2011
Externally publishedYes

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Synovial Sarcoma
Melanoma
Lymphocytes
Neoplasms
T-Cell Antigen Receptor
T-Lymphocytes
Tumor-Infiltrating Lymphocytes
Adoptive Immunotherapy
Therapeutics
T-Cell Receptor Genes
Testicular Neoplasms
Genetic Therapy
Interleukin-2

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. / Robbins, Paul F.; Morgan, Richard A.; Feldman, Steven A.; Yang, James C.; Sherry, Richard M.; Dudley, Mark E.; Wunderlich, John R.; Nahvi, Azam V.; Helman, Lee J.; Mackall, Crystal L.; Kammula, Udai S.; Hughes, Marybeth S.; Restifo, Nicholas P.; Raffeld, Mark; Lee, Chyi Chia Richard; Levy, Catherine L.; Li, Yong F.; El-Gamil, Mona; Schwarz, Susan L.; Laurencot, Carolyn; Rosenberg, Steven A.

In: Journal of Clinical Oncology, Vol. 29, No. 7, 01.03.2011, p. 917-924.

Research output: Contribution to journalArticle

Robbins, PF, Morgan, RA, Feldman, SA, Yang, JC, Sherry, RM, Dudley, ME, Wunderlich, JR, Nahvi, AV, Helman, LJ, Mackall, CL, Kammula, US, Hughes, MS, Restifo, NP, Raffeld, M, Lee, CCR, Levy, CL, Li, YF, El-Gamil, M, Schwarz, SL, Laurencot, C & Rosenberg, SA 2011, 'Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1', Journal of Clinical Oncology, vol. 29, no. 7, pp. 917-924. https://doi.org/10.1200/JCO.2010.32.2537
Robbins, Paul F. ; Morgan, Richard A. ; Feldman, Steven A. ; Yang, James C. ; Sherry, Richard M. ; Dudley, Mark E. ; Wunderlich, John R. ; Nahvi, Azam V. ; Helman, Lee J. ; Mackall, Crystal L. ; Kammula, Udai S. ; Hughes, Marybeth S. ; Restifo, Nicholas P. ; Raffeld, Mark ; Lee, Chyi Chia Richard ; Levy, Catherine L. ; Li, Yong F. ; El-Gamil, Mona ; Schwarz, Susan L. ; Laurencot, Carolyn ; Rosenberg, Steven A. / Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. In: Journal of Clinical Oncology. 2011 ; Vol. 29, No. 7. pp. 917-924.
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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.",
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T1 - Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1

AU - Robbins, Paul F.

AU - Morgan, Richard A.

AU - Feldman, Steven A.

AU - Yang, James C.

AU - Sherry, Richard M.

AU - Dudley, Mark E.

AU - Wunderlich, John R.

AU - Nahvi, Azam V.

AU - Helman, Lee J.

AU - Mackall, Crystal L.

AU - Kammula, Udai S.

AU - Hughes, Marybeth S.

AU - Restifo, Nicholas P.

AU - Raffeld, Mark

AU - Lee, Chyi Chia Richard

AU - Levy, Catherine L.

AU - Li, Yong F.

AU - El-Gamil, Mona

AU - Schwarz, Susan L.

AU - Laurencot, Carolyn

AU - Rosenberg, Steven A.

PY - 2011/3/1

Y1 - 2011/3/1

N2 - 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.

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