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

• C. Yee

  Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, D3-100, Seattle, WA 98109 and Department of Medicine, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195; and Department of Immunology, Mayo Clinic, 200 1st Southwest, Rochester, MN 55905

• J. A. Thompson

  Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, D3-100, Seattle, WA 98109 and Department of Medicine, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195; and Department of Immunology, Mayo Clinic, 200 1st Southwest, Rochester, MN 55905

• D. Byrd

  Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, D3-100, Seattle, WA 98109 and Department of Medicine, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195; and Department of Immunology, Mayo Clinic, 200 1st Southwest, Rochester, MN 55905

• S. R. Riddell

  Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, D3-100, Seattle, WA 98109 and Department of Medicine, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195; and Department of Immunology, Mayo Clinic, 200 1st Southwest, Rochester, MN 55905

• P. Roche

  Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, D3-100, Seattle, WA 98109 and Department of Medicine, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195; and Department of Immunology, Mayo Clinic, 200 1st Southwest, Rochester, MN 55905

• E. Celis

  Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, D3-100, Seattle, WA 98109 and Department of Medicine, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195; and Department of Immunology, Mayo Clinic, 200 1st Southwest, Rochester, MN 55905

• P. D. Greenberg

  Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, D3-100, Seattle, WA 98109 and Department of Medicine, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195; and Department of Immunology, Mayo Clinic, 200 1st Southwest, Rochester, MN 55905

抄録

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 × 10 6 units/m 2 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.

収録刊行物

• Proceedings of the National Academy of Sciences

  Proceedings of the National Academy of Sciences 99 (25), 16168-16173, 2002-11-11

  Proceedings of the National Academy of Sciences

キーワード

• Multidisciplinary

詳細情報

• CRID: 1360292621012398080
• NII論文ID: 80015732438
• DOI: 10.1073/pnas.242600099
• ISSN: 10916490
• ISSN: 00278424
• Web Site: https://pnas.org/doi/pdf/10.1073/pnas.242600099
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