Large scale expansion of gamma 9 delta 2 T lymphocytes: Innacell gamma delta cell therapy product

• Published in: Journal of immunological methods 2007-09, Vol.326 (1-2), p.63-75
• Main Authors: Salot, Samuel, Laplace, Catherine, Saïagh, Soraya, Bercegeay, Sylvain, Tenaud, Isabelle, Cassidanius, Alain, Romagne, François, Dreno, Brigitte, Tiollier, Jérôme
• Format: Article
• Language: English
• Subjects: Carcinoma, Renal Cell - immunology; Carcinoma, Renal Cell - metabolism; Carcinoma, Renal Cell - secondary; Carcinoma, Renal Cell - therapy; Cell Proliferation; Cells, Cultured; Humans; Immunotherapy, Adoptive; Leukapheresis; Lymphocyte Count; Receptors, Antigen, T-Cell, gamma-delta - therapeutic use; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - transplantation
• ISSN: 0022-1759
• DOI: 10.1016/j.jim.2007.07.010

gamma9delta2 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 gamma9delta2 T lymphocytes does not depend on the expression of major histocompatibility complex molecules by target tumour cells. INNACELL gammadeltatrade mark is a cell therapy product obtained by ex vivo amplification of mononuclear cells. The stimulation is achieved by a specific synthetic agonist of gamma9delta2 T lymphocytes, bromohydrin pyrophosphate (BrHPP). After a single stimulation with BrHPP, gamma9delta2 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 gamma9delta2 T lymphocytes undergo a specific 1000-fold expansion, corresponding to a gamma9delta2 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 gamma9delta2 subset, which then becomes predominant in the cell culture in large amounts.