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Adoptive cell transfer ACT of tumor-specific T lymphocytes represents a relevant therapeutic strategy to treat metastatic melanoma patients. Ideal T-cells should combine tumor specificity and reactivity with survival in vivo, while avoiding autoimmune side effects. Each patient received a combination of Melan-A and MELOE-1 polyclonal specific T-cells, whose specificity and anti-tumor reactivity were checked prior to injection, with subcutaneous IL Transferred T-cells were also characterized in terms of functional avidity, diversity and phenotype and their blood persistence was evaluated.
An increase in specific T-cells was detected in the blood of all patients at day 1 and progressively disappeared from day 7 onwards. No serious adverse events occurred after this ACT. Clinically, five patients progressed and one patient experienced a partial response following therapy. One possible reason for the therapeutic failure of ICIs in a significant proportion of patients may be the lack of a tumor-specific T-repertoire that can be mobilized by anti-IC antibodies.
In this context, adoptive transfer of tumor-specific T cells could be a realistic option, especially in combination with ICI. For these strategies, ideal effector T-cells should combine different properties, such as tumor specificity and reactivity together with survival and tumor infiltration after transfer to autologous patients.
The lack of therapeutic efficacy in the other half of patients may have resulted from the injection of poorly reactive T cell clones in vivo due to the exhaustion status of infused T cells.
