title: White paper on adoptive cell therapy for cancer with tumor-infiltrating lymphocytes: a report of the CTEP subcommittee on adoptive cell therapy.
abstract: Adoptive T-cell therapy (ACT) using expanded autologous tumor-infiltrating lymphocytes (TIL) and tumor antigen-specific T cell expanded from peripheral blood are complex but powerful immunotherapies directed against metastatic melanoma. A number of nonrandomized clinical trials using TIL combined with high-dose interleukin-2 (IL-2) have consistently found clinical response rates of 50% or more in metastatic melanoma patients accompanied by long progression-free survival. Recent studies have also established practical methods for the expansion of TIL from melanoma tumors with high success rates. These results have set the stage for randomized phase II/III clinical trials to determine whether ACT provides benefit in stage IV melanoma. Here, we provide an overview of the current state-of-the art in T-cell-based therapies for melanoma focusing on ACT using expanded TIL and address some of the key unanswered biological and clinical questions in the field. Different phase II/III randomized clinical trial scenarios comparing the efficacy of TIL therapy to high-dose IL-2 alone are described. Finally, we provide a roadmap describing the critical steps required to test TIL therapy in a randomized multicenter setting. We suggest an approach using centralized cell expansion facilities that will receive specimens and ship expanded TIL infusion products to participating centers to ensure maximal yield and product consistency. If successful, this approach will definitively answer the question of whether ACT can enter mainstream treatment for cancer.
authors.affiliation: Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA. jeffrey.weber@moffitt.org
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Weber
authors.forename: Michael
authors.initials: M
authors.lastname: Atkins
authors.forename: Patrick
authors.initials: P
authors.lastname: Hwu
authors.forename: Laszlo
authors.initials: L
authors.lastname: Radvanyi
authors.forename: Mario
authors.initials: M
authors.lastname: Sznol
authors.forename: Cassian
authors.initials: C
authors.lastname: Yee
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D002986:Clinical Trials as Topic; D006801:Humans; D016219:Immunotherapy, Adoptive; D007938:Leukemia / Q000276:immunology / Q000628:therapy; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000637:transplantation*; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D005791:Patient Care