Successful adoptive transfer and in vivo expansion of haploidentical γδ T cells

Journal of Translational Medicine

Volker Kunzmann²  Hermann Einsele²  Josef Birkmann¹  Brigitte Kimmel²  Kerstin Schaefer-Eckart¹  Manfred Smetak¹  Martin Wilhelm¹ 

[1] Klinikum Nürnberg, Medizinische Klinik 5, Prof-Ernst-Nathan-Str. 1, D-90340 Nuernberg, Germany;Medizinische Klinik und Poliklinik II Wuerzburg, University of Wuerzburg, Wuerzburg, Germany

关键词: in vivo cell expansion;    Adoptive transfer;    Innate immunity;    Bisphosphonate;    Interleukin-2;    NK cells;    Haploidentical γδ T lymphocytes;   

Others  :  817943
DOI  :  10.1186/1479-5876-12-45

 received in 2013-11-12, accepted in 2014-01-30,  发布年份 2014

【 摘 要 】

Background

The primary aim of this pilot study was to determine the feasibility and safety of an adoptive transfer and in vivo expansion of human haploidentical γδ T lymphocytes.

Methods

Patients with advanced haematological malignancies who are not eligible for allogeneic transplantation received peripheral blood mononuclear cells from half-matched family donors. For that, a single unstimulated leukapheresis product was incubated with both the anti-CD4 and anti-CD8 antibodies conjugated to paramagnetic particles. The depletion procedure was performed on a fully automated CliniMACS® device according to the manufacturer’s instructions. On average, patients received 2.17 × 10⁶/kg (range 0.9-3.48) γδ T cells with <1% CD4- or CD8-positive cells remaining in the product. All patients received prior lymphopenia-inducing chemotherapy (fludarabine 20-25 mg/m² day -6 until day -2 and cyclophosphamide 30-60 mg/kg day -6 and -5) and were treated with 4 mg zoledronate on day 0 and 1.0x10⁶ IU/m² IL-2 on day +1 until day +6 for the induction of γδ T cell proliferation in vivo.

Results

This resulted in a marked in vivo expansion of donor γδ T cells and, to a lower extent, natural killer cells and double-negative αβ T cells (mean 68-fold, eight-fold, and eight-fold, respectively). Proliferation peaked by around day +8 and donor cells persisted up to 28 days. Although refractory to all prior therapies, three out of four patients achieved a complete remission, which lasted for 8 months in a patient with plasma cell leukaemia. One patient died from an infection 6 weeks after treatment.

Conclusion

This pilot study shows that adoptive transfer and in vivo expansion of haploidentical γδ T lymphocytes is feasible and suggests a potential role of these cells in the treatment of haematological diseases.

【 授权许可】

   
2014 Wilhelm et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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