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

Abstract : 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. 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 coexpressing 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.
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Contributor : Nathalie LABARRIERE Connect in order to contact the contributor
Submitted on : Tuesday, June 15, 2021 - 10:56:08 AM
Last modification on : Tuesday, May 24, 2022 - 2:30:52 PM
Long-term archiving on: : Thursday, September 16, 2021 - 6:26:17 PM


Dreno et al., 2021.pdf
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Brigitte Dréno, Amir Khammari, Agnès Fortun, Virginie Vignard, Soraya Saiagh, et al.. Phase I/II clinical trial of adoptive cell transfer of sorted specific T cells for metastatic melanoma patients. Cancer Immunology, Immunotherapy, Springer Verlag, 2021, Online ahead of print. ⟨10.1007/s00262-021-02961-0⟩. ⟨inserm-03260784⟩



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