Human γδ T cells as mediators of chimaeric-receptor redirected anti-tumour immunity

Markus Rischer, Sibylle Pscherer, Susanne Duwe, Josef Vormoor, Heribert Jürgens, Claudia Rossig

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

92 Citaten (Scopus)


Human peripheral blood γδ T cells (Vγ9+ Vδ2+) can be selectively expanded in vivo by the systemic administration of aminobisphosphonates without prior antigen priming. To assess the potential of human γδ T cells to serve as effector cells of specific anti-tumour immunity, we expanded peripheral blood-derived γδ T cells and transduced them with recombinant retrovirus encoding GD2- 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 γδ T cell population (Vγ9+ Vδ2+ 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 γδ T cells efficiently recognized antigen-expressing tumour cell targets, as demonstrated by target-specific upregulation of CD69 and secretion of interferon-α. Moreover, transduced γδ 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 γδ 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.

Originele taal-2Engels
Pagina's (van-tot)583-592
Aantal pagina's10
TijdschriftBritish Journal of Haematology
Nummer van het tijdschrift4
StatusGepubliceerd - aug. 2004
Extern gepubliceerdJa


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