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Human γδ T cells as mediators of chimaeric‐receptor redirected anti‐tumour immunity
Author(s) -
Rischer Markus,
Pscherer Sibylle,
Duwe Susanne,
Vormoor Josef,
Jürgens Heribert,
Rossig Claudia
Publication year - 2004
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2004.05077.x
Subject(s) - biology , cytotoxic t cell , population , streptamer , antigen , il 2 receptor , interleukin 21 , t cell , adoptive cell transfer , immunology , cd8 , priming (agriculture) , antigen presenting cell , microbiology and biotechnology , immune system , in vitro , medicine , biochemistry , botany , germination , environmental health
Summary Human peripheral blood γ δ T cells (V γ 9 + V δ 2 + ) can be selectively expanded in vivo by the systemic administration of aminobisphosphonates without prior antigen priming. To assess the potential of human γ δ T cells to serve as effector cells of specific anti‐tumour immunity, we expanded peripheral blood‐derived γ δ T cells and transduced them with recombinant retrovirus encoding G D2 ‐ or CD19‐specific chimaeric receptors. Flow cytometric analysis of T cells from four individual donors cultured in the presence of zoledronate at day 14 of culture showed selective enrichment of the γ δ T cell population (V γ 9 + V δ 2 + CD3 + CD4 − CD8 − ) to 73–96% of total CD3 + T cells. Retroviral gene transfer resulted in chimaeric receptor surface expression in 73 ± 12% of the population. Transduced γ δ T cells efficiently recognized antigen‐expressing tumour cell targets, as demonstrated by target‐specific upregulation of CD69 and secretion of interferon‐ α . Moreover, transduced γ δ T cells efficiently and specifically lysed the antigen‐expressing tumour targets. They could be efficiently expanded in vitro and maintained in culture for prolonged periods. Zoledronate‐activated human γ δ T cells expressing chimaeric receptors may thus serve as potent and specific anti‐tumour effector cells. Their responsiveness to stimulation with aminobisphosphonates may enable the selective re‐expansion of adoptively transferred T cells in vivo , permitting long lasting anti‐tumour immune control.