Large scale expansion of γ9δ2 T lymphocytes: Innacell γδ™ cell therapy product

γ9δ2 T lymphocytes are non-conventional lymphocytes presenting a direct cytotoxic effect against a broad range of tumour targets. These cells also secrete inflammatory cytokines that can boost the other components of the immune system. In contrast to conventional CD8+ T cells, the cytotoxic effect of γ9δ2 T lymphocytes does not depend on the expression of major histocompatibility complex molecules by target tumour cells. INNACELL γδ™ is a cell therapy product obtained by ex vivo amplification of mononuclear cells. The stimulation is achieved by a specific synthetic agonist of γ9δ2 T lymphocytes, bromohydrin pyrophosphate (BrHPP). After a single stimulation with BrHPP, γ9δ2 T lymphocytes are expanded for 2 weeks in a closed system in culture medium with interleukin-2 (IL-2). On day 15, cells are washed and harvested in 4% human serum albumin. In this manufacturing process, the total cell population is expanded by approximately 10-fold and γ9δ2 T lymphocytes undergo a specific 1000-fold expansion, corresponding to a γ9δ2 T lymphocyte enrichment of more than 70% at the end of the culture. This manufacturing process is much simpler than most current cellular therapy approaches using conventional CD8+ T-cell lines or clones: there is no final or initial separation, no purification step and no use of feeder cells; the specific T-cell receptor-mediated signal provided by BrHPP is sufficient to trigger the IL-2-dependent expansion of the γ9δ2 subset, which then becomes predominant in the cell culture in large amounts.