Phase I/II clinical trial of adoptive cell transfer of sorted specific T cells for metastatic melanoma patients

• DOI: 10.1007/s00262-021-02961-0
• Publication Date: 2021-06-12T21:02:44Z
• Authors: Brigitte Dréno; Amir Khammari; Agnès Fortun; Virginie Vignard; Soraya Saiagh; Tiffany Beauvais; Nicolas Jouand; Sylvain Bercegay; Sylvain Simon; François Lang; Nathalie Labarrière
• Keywords: Adult; 0301 basic medicine; MELOE-1; T-Lymphocytes; Melan-A; 610; [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy; Middle Aged; Immunotherapy, Adoptive; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Clinical Trial Report; Cell Line, Tumor; 616; Adoptive cell transfer; Humans; [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy; Melanoma; TCR; Aged

AbstractAdoptive 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. Here we report results from a Phase I/II clinical trial (NCT02424916, performed between 2015 and 2018) in which 6 metastatic HLA-A2 melanoma patients received autologous antigen-specific T-cells produced from PBMC, after peptide stimulation in vitro, followed by sorting with HLA-peptide multimers and amplification. 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-2. 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. Melan-A and MELOE-1 specific T-cells infused to this patient were diverse, of high avidity, with a high proportion of T lymphocytes co-expressing PD-1 and TIGIT but few other exhaustion markers. In conclusion, we demonstrated the feasibility and safety of ACT with multimer-sorted Melan-A and MELOE-1 specific T cells to metastatic melanoma patients. The clinical efficacy of such therapeutic strategy could be further enhanced by the selection of highly reactive T-cells, based on PD-1 and TIGIT co-expression, and a combination with ICI, such as anti-PD-1.