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?

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.