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Cell transfer immunotherapy for metastatic solid cancer—what clinicians need to know

Nature Reviews Clinical Oncology volume 8, pages 577–585 (2011)Cite this article

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Abstract

Cancer immunotherapy using the adoptive transfer of autologous tumor-infiltrating lymphocytes results in objective cancer regression in 49–72% of patients with metastatic melanoma. In a pilot trial combining cell transfer with a maximum lymphodepleting regimen, complete durable responses were seen in 40% of patients, with complete responses ongoing beyond 3 to 7 years. Current approaches to cell transfer therapy using autologous cells genetically engineered to express conventional or chimeric T-cell receptors have mediated cancer regression in patients with metastatic melanoma, synovial sarcoma, neuroblastoma and refractory lymphoma. Adoptive cell transfer immunotherapy is a rapidly developing new approach to the therapy of metastatic cancer in humans. This Review will emphasize the current available applications of cell transfer immunotherapy for patients with cancer.

Key Points

  • Adoptive cell transfer immunotherapy can mediate the objective regression of metastatic melanoma in 49–72% of patients

  • Complete durable regressions using cell transfer immunotherapy have been seen in up to 40% of patients and it is likely curative in many patients

  • The high incidence of durable complete regressions in patients with melanoma receiving cell transfer immunotherapy is similar, independent of the patient's prior treatment

  • Cell transfer immunotherapy can be extended to additional cancer types by using autologous lymphocytes that are genetically transduced to express antitumor T-cell receptors (TCRs) or chimeric antigen receptors (CARs)

  • Using these TCR or CAR gene transduced cells, objective regressions have been seen in patients with synovial cell sarcoma, lymphoma, and melanoma

  • The opportunity to genetically modify autologous lymphocytes with a variety of genes that can improve their antitumor function is opening new possibilities for developing effective cancer treatments

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Figure 1: Adoptive cell transfer immunotherapy using either autologous TILs obtained from resected tumors or using peripheral lymphocytes genetically transduced with retroviruses to express antitumor T-cell receptors.
Figure 2: Preparative regimens for cell transfer.
Figure 3: Survival of patients with metastatic melanoma treated with autologous tumor-infiltrating lymphocytes.
Figure 4: Examples of complete durable responses in patients receiving adoptive cell therapy.3
Figure 5: Expression of three cancer–testes antigens (NY-ESO-1, MAGE-A1, MAGE-A3) in a variety of cancer types.
Figure 6: Examples of cancer regression in patients with synovial cell sarcoma treated with autologous T cells transduced with the gene encoding an anti-NY-ESO-1 T-cell receptor.

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Acknowledgements

C. P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape, LLC-accredited continuing medical education activity associated with this article.

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  1. Surgery Branch, National Cancer Institute, National Institutes of Health, CRC-Building 10, Room 3-3940, 10 Center Drive, Bethesda, 20892–1201, MD, USA

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Rosenberg, S. Cell transfer immunotherapy for metastatic solid cancer—what clinicians need to know. Nat Rev Clin Oncol 8, 577–585 (2011). https://doi.org/10.1038/nrclinonc.2011.116

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