Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: In vivo persistence, migration, and antitumor effect of transferred T cells

C. Yee, J. A. Thompson, D. Byrd, S. R. Riddell, P. Roche, E. Celis, P. D. Greenberg

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913 Citations (Scopus)

Abstract

Adoptive T cell therapy, involving the ex vivo selection and expansion of antigen-specific T cell clones, provides a means of augmenting antigen-specific immunity without the in vivo constraints that can accompany vaccine-based strategies. A phase I study was performed to evaluate the safety, in vivo persistence, and efficacy of adoptively transferred CD8+ T cell clones targeting the tumor-associated antigens. MART1/MelanA and gp100 for the treatment of patients with metastatic melanoma. Four infusions of autologous T cell clones were administered, the first without IL-2 and subsequent infusions with low-dose IL-2 (at 0.25, 0.50, and 1.0 × 106 units/m2 twice daily for the second, third, and fourth infusions, respectively). Forty-three infusions of MART1/MelanA-specific or gp100-specific CD8+ T cell clones were administered to 10 patients. No serious toxicity was observed. We demonstrate that the adoptively transferred T cell clones persist in vivo in response to low-dose IL-2, preferentially localize to tumor sites and mediate an antigen-specific immune response characterized by the elimination of antigen-positive tumor cells, regression of individual metastases, and minor, mixed or stable responses in 8 of 10 patients with refractory, metastatic disease for up to 21 mo.

Original languageEnglish (US)
Pages (from-to)16168-16173
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number25
DOIs
StatePublished - Dec 10 2002

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CD8 Antigens
Cell- and Tissue-Based Therapy
Melanoma
Clone Cells
T-Lymphocytes
MART-1 Antigen
Interleukin-2
Neoplasm Antigens
Therapeutics
Antigens
Histocompatibility Antigens Class II
Immunity
Vaccines
Neoplasm Metastasis
Safety
Neoplasms

ASJC Scopus subject areas

  • General

Cite this

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abstract = "Adoptive T cell therapy, involving the ex vivo selection and expansion of antigen-specific T cell clones, provides a means of augmenting antigen-specific immunity without the in vivo constraints that can accompany vaccine-based strategies. A phase I study was performed to evaluate the safety, in vivo persistence, and efficacy of adoptively transferred CD8+ T cell clones targeting the tumor-associated antigens. MART1/MelanA and gp100 for the treatment of patients with metastatic melanoma. Four infusions of autologous T cell clones were administered, the first without IL-2 and subsequent infusions with low-dose IL-2 (at 0.25, 0.50, and 1.0 × 106 units/m2 twice daily for the second, third, and fourth infusions, respectively). Forty-three infusions of MART1/MelanA-specific or gp100-specific CD8+ T cell clones were administered to 10 patients. No serious toxicity was observed. We demonstrate that the adoptively transferred T cell clones persist in vivo in response to low-dose IL-2, preferentially localize to tumor sites and mediate an antigen-specific immune response characterized by the elimination of antigen-positive tumor cells, regression of individual metastases, and minor, mixed or stable responses in 8 of 10 patients with refractory, metastatic disease for up to 21 mo.",
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T2 - In vivo persistence, migration, and antitumor effect of transferred T cells

AU - Yee, C.

AU - Thompson, J. A.

AU - Byrd, D.

AU - Riddell, S. R.

AU - Roche, P.

AU - Celis, E.

AU - Greenberg, P. D.

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