Large scale expansion of gamma 9 delta 2 T lymphocytes: Innacell gamma delta cell therapy product.
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.
Salot
Samuel
S
Innate Pharma, 119-121 Ancien chemin de Cassis, 13009 Marseille, France. samuel.salot@innate-pharma.fr
Laplace
Catherine
C
Saïagh
Soraya
S
Bercegeay
Sylvain
S
Tenaud
Isabelle
I
Cassidanius
Alain
A
Romagne
François
F
Dreno
Brigitte
B
Tiollier
Jérôme
J
D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000378:metabolism / Q000556:secondary / Q000628:therapy; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D016219:Immunotherapy, Adoptive; D007937:Leukapheresis; D018655:Lymphocyte Count; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000627:therapeutic use*; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation
D016692:Receptors, Antigen, T-Cell, gamma-delta; C521523:T-cell receptor Vdelta2, human; C521522:T-cell receptor Vgamma9, human