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

Abstract

BackgroundThe 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.MethodsPatients 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.ResultsThis 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.ConclusionThis 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.

Adoptively transferred Vγ9Vδ2 T cells show potent antitumor effects in a preclinical B cell lymphomagenesis model

“…In another trial involving 18 subjects with metastatic solid tumors who received adoptive transfer of Zometa-expanded γδ T cells in combination with Zometa and IL-2, three patients showed measurable disease responses (49). Finally, in a trial of 4 patients with advanced hematological malignancies who received haploidentical transplants highly enriched for γδ T cells followed by in vivo administration of Zometa and IL-2, three subjects showed complete remission lasting more than 6 months while one died of an infection 6 weeks after the cell transfusion (50).…”

Adoptive Immunotherapy of Epithelial Ovarian Cancer with Vγ9Vδ2 T Cells, Potentiated by Liposomal Alendronic Acid

“…Adoptive immunotherapy using haploidentical purified gd T cells has recently achieved impressive results in a small-scale clinical study in lymphodepleted patients with treatment-refractory hematologic malignancy (36). Furthermore, Cooper et al (37) have developed an efficient K562-based feeder system that expands polyclonal gd T cells with cytolytic activity against tumor cells and derived xenografts that are naturally sensitive to these cells.…”

Adaptive Immune-like γ/δ T Lymphocytes Share Many Common Features with Their α/β T Cell Counterparts

“…These techniques have been transitioned to the clinic for investigational treatments of cancer (56,57). It has been observed that adoptive transfer and in vivo expansions of different g/d T cell subsets (Vg9Vd2, Vd1, or other non-Vg9Vd2 T cells) are safe therapeutic modalities and can result in objective clinical responses in the treatment of cancer such as renal cell carcinoma (58), colorectal cancer, and melanoma (59) or leukemia (60).…”