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

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.

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. Cells are expanded in vitro to large numbers (up to 10¹¹) and infused after patients have received a preparative lymphodepleting regimen. Abbreviations: TCR, T-cell receptor; TIL, tumor-infiltrating lymphocyte.

Figure 2 |

Preparative regimens for cell transfer. A comparison of the lymphodepleting methods used: non-myeloablative and TBI (using 2 Gy and 12 Gy). Abbreviations: Cy, cyclophosphamide; Flu, fludarabine; IL, interleukin; TBI, total body irradiation.

Figure 3 |

Survival of patients with metastatic melanoma treated with autologous tumor-infiltrating lymphocytes. Patients were treated in three sequential trials using a cyclophosphamide–fludarabine lymphodepleting regimen either alone (no TBI) or plus 2 Gy or 12 Gy TBI (Figure 2). Median follow up of 69 months. Abbreviation: TBI, total body irradiation.

Figure 4 |

Examples of complete durable responses in patients receiving adoptive cell therapy. a | Regression of multiple liver metastases (patient received non-myeloablative lymphodepletion; Figure 2). b | Regression of multiple lung metastases and an adrenal metastasis (patient received total body irradiation 12 Gy lymphodepletion; Figure 2). Permission obtained from the American Association for Cancer Research © Rosenberg, S. A. et al. Clin. Cancer Res. 17, 4550–4557 (2011).

Figure 5 |

Expression of three cancer–testes antigens (NY-ESO-1, MAGE-A1, MAGE-A3) in a variety of cancer types. Abbreviations: HCC, hepatocellular carcinoma; NSCLC, non-small-cell lung cancer.

Figure 6 |

Examples of cancer regression in patients with synovial cell sarcoma treated with autologous T cells transduced with the gene encoding an anti-NYESO-1 T-cell receptor. a | Regression of multiple lung metastases. B | Regression of multiple lung and liver metastases. Permission for part a obtained from the American Society of Clinical Oncology © Robbins, P. F. et al. J. Clin. Oncol. 29, 917–924 (2011).