Adoptive Cell Therapy for the Treatment of Patients with Metastatic Melanoma

By S. Rosenberg, M. Dudley. Current Opinion in Immunology, 2009

626 citations recorded by the source corpus.

Adoptive cell therapy (ACT) is the best available treatment for patients with metastatic melanoma. In a recent series of three consecutive clinical trials using increasing lymphodepletion prior to infusion of autologous tumor infiltrating lymphocytes (TIL), objective response rates between 49% and 72% were seen. Persistence of infused cells in the circulation at one month was highly correlated with anti-tumor response as was the mean telomere length of the cells infused and the number of CD8+ CD27+ cells infused. Responses occur at all sites and appear to be durable with many patients in ongoing response beyond three years. In the most recent trial of 25 patients receiving maximum lymphodepletion, seven of the 25 patients (28%) achieved a complete response. Of the 12 patients in the three trials who achieved a complete response all but one are ongong between 18 and 75 months. We recently demonstrated that ACT using autologous lymphocytes genetically modified to express anti-tumor T cell receptors can mediate tumor regression and this approach is now being applied to patients with common epithelial cancers.

Subfields: Genetics, Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/0e0b0f1ff2fc0faf9e15a43d824d3ac8bce84699

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Citations in the corpus

Cancer immunotherapy (2012, background): “Initial efforts at adoptive T cell therapy began with melanoma and met with limited success (Rosenberg et al., 1993).”
Immune parameters affecting the efficacy of chemotherapeutic regimens (2011, methodology): “They used adoptive T-cell transfer to treat advanced melanoma and T-cell alloreactivities that mediated a protective graft-versus-leukemia effect in the course of an allogeneic hematopoietic stem-cell transplantation for leukemias”
Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. (2011, background): “49% to 72% of patients with metastatic melanoma.(1,2) The observation that melanoma-reactive”
Exhaustion of tumor-specific CD8⁺ T cells in metastases from melanoma patients. (2011, background): “Circulating human tumor-specific CD8+ T cells may be cytotoxic and produce cytokines in vivo (19–21), indicating that self- and tumor-specific human CD8+ T cells can reach functional competence after potent immunotherapy such as vaccination with peptide, incomplete Freund’s adjuvant (IFA), and CpG (”
Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells (2011, background): “Nonetheless, combination therapies that link ACT with treatment targeting the mechanisms of local immunosuppression, such as lymphodepletion of the host by either irradiation or chemotherapy before cell transfer, promise to overcome this obstacle and are being actively pursued (Rosenberg and Dudley,”
Novel cancer immunotherapy agents with survival benefit: recent successes and next steps (2011, background): “Other immunotherapy strategies, including ACT whereby T cells are administered to patient”