title: Achievements and challenges of adoptive T cell therapy with tumor-infiltrating or blood-derived lymphocytes for metastatic melanoma: what is needed to achieve standard of care?
abstract: Adoptive cell therapy (ACT) based on autologous T cell derived either from tumor as tumor-infiltrating lymphocytes (TILs) or from peripheral blood is developing as a key area of future personalized cancer therapy. TIL-based ACT is defined as the infusion of T cells harvested from autologous fresh tumor tissues after ex vivo activation and extensive expansion. TIL-based ACT has so far only been tested in smaller phase I/II studies, but these studies consistently confirm an impressive clinical response rate of up to 50 % in metastatic melanoma including a significant proportion of patients with durable complete tumor eradication. These remarkable results justify the need for a definitive phase III trial documenting the efficacy of this type of T cell-based Advanced Therapy Medicinal Product in order to pave the way for regulatory approval and implementation of TIL therapy as a new treatment standard in oncology practice. TIL-based ACT can, however, only be offered to a limited group of patients based on the need for accessible tumor tissue, the complexity of TIL production procedures, and the very intensive nature of this three-step treatment including both high-dose chemotherapy and interleukin-2 in addition to T cell infusion. To this end, adoptive T cell therapy using peripheral blood mononuclear cell-derived T cells could be a welcome alternative to circumvent these limitations and broaden up the applicability of ACT. Here, we discuss current initiatives in this focused research review.
authors.affiliation: Department of Haematology and Department of Oncology, Herlev Hospital, Center for Cancer Immune Therapy (CCIT), University of Copenhagen, Herlev Ringvej 75, 2730, Herlev, Denmark, Inge.Marie.Svane@regionh.dk.
authors.forename: Inge Marie
authors.initials: IM
authors.lastname: Svane
authors.forename: Els M
authors.initials: EM
authors.lastname: Verdegaal
mesh_terms: D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods* / Q000592:standards*; D017710:Lymphocyte Transfusion / Q000379:methods*; D008214:Lymphocytes / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000637:transplantation*; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic; D059039:Standard of Care
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