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 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.

• Authors: Brigitte Dréno, Amir Khammari, Agnès Fortun, Virginie Vignard, Soraya Saiagh, Tiffany Beauvais, Nicolas Jouand, Sylvain Bercegay, Sylvain Simon, François Lang, Nathalie Labarrière
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 70 Issue 10 Pg. 3015-3030 (Oct 2021) ISSN: 1432-0851 [Electronic] Germany
• PMID: 34120214 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article)
• Copyright: © 2021. The Author(s).

Topics

• Adult
• Aged
• Cell Line, Tumor
• Humans
• Immunotherapy, Adoptive (methods)
• Melanoma (immunology)
• Middle Aged
• T-Lymphocytes (metabolism)