2008 April ; 8(4): 299–308 | Steven A. Rosenberg, Nicholas P. Restifo, James C. Yang, Richard A. Morgan, and Mark E. Dudley
Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes has emerged as the most effective treatment for patients with metastatic melanoma, achieving objective cancer regression in approximately 50% of patients. The use of donor lymphocytes for ACT is also effective for immunosuppressed patients who develop post-transplant lymphomas. Recent studies have demonstrated that genetic engineering of human lymphocytes to recognize cancer antigens and mediate cancer regression in vivo opens new possibilities for extending ACT immunotherapy to a wide range of cancer types. ACT involves identifying and expanding anti-tumor lymphocytes ex vivo, followed by their reinfusion into the patient. Key components of ACT include lymphodepletion before cell transfer to eliminate regulatory T cells and endogenous lymphocytes that compete for homeostatic cytokines. ACT has shown substantial theoretical and practical advantages over other immunotherapy approaches, such as non-specific immunomodulation and active immunization. Clinical trials have demonstrated the effectiveness of ACT in treating metastatic melanoma, with durable responses observed in multiple metastatic sites. The success of ACT in melanoma has led to the development of gene-modified lymphocytes, which can be directed against a broad array of cancer antigens. These advancements suggest that ACT has the potential to revolutionize cancer treatment, particularly for common epithelial cancers. However, the personalized nature of ACT presents challenges in commercialization and integration into current oncological practices.Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes has emerged as the most effective treatment for patients with metastatic melanoma, achieving objective cancer regression in approximately 50% of patients. The use of donor lymphocytes for ACT is also effective for immunosuppressed patients who develop post-transplant lymphomas. Recent studies have demonstrated that genetic engineering of human lymphocytes to recognize cancer antigens and mediate cancer regression in vivo opens new possibilities for extending ACT immunotherapy to a wide range of cancer types. ACT involves identifying and expanding anti-tumor lymphocytes ex vivo, followed by their reinfusion into the patient. Key components of ACT include lymphodepletion before cell transfer to eliminate regulatory T cells and endogenous lymphocytes that compete for homeostatic cytokines. ACT has shown substantial theoretical and practical advantages over other immunotherapy approaches, such as non-specific immunomodulation and active immunization. Clinical trials have demonstrated the effectiveness of ACT in treating metastatic melanoma, with durable responses observed in multiple metastatic sites. The success of ACT in melanoma has led to the development of gene-modified lymphocytes, which can be directed against a broad array of cancer antigens. These advancements suggest that ACT has the potential to revolutionize cancer treatment, particularly for common epithelial cancers. However, the personalized nature of ACT presents challenges in commercialization and integration into current oncological practices.