Adoptive cellular therapy using cells enriched for NKG2D+CD3+CD8+T cells after autologous transplantation for myeloma

Abstract

The number of circulating lymphocytes on day 15 after transplantation correlates with improved survival in patients with myeloma, but the lymphocyte subset responsible is unknown. NKG2D is a natural killer (NK) cell activating receptor that mediates non-MHC restricted and TCR-independent cell lysis. Our preliminary results indicate that CD3(+)CD8(+) T cells expressing NKG2D may be a critical lymphocyte population. A phase II trial examined the feasibility of infusing ex vivo-expanded cells enriched for NKG2D(+)CD3(+)CD8(+) T cells at weeks 1, 2, 4, and 8 after an autologous transplantation. In addition, low-dose IL-2 (6 × 10(5) IU/m(2)/day) was administered for 4 weeks, beginning on the day of transplantation. Twenty-three patients were accrued and 19 patients are evaluable. There were no treatment-related deaths. All patients completed their course of IL-2 and demonstrated normal engraftment. When compared with patients with myeloma who underwent transplantation not receiving posttransplantation immune therapy, the treated patients demonstrated an increase in the number of circulating NKG2D(+)CD3(+)CD8(+) T cells/μL (P < .004), CD3(+)CD8(+) T cells/μL (P < .04), CD3(+)CD8(+)CD56(+) T cells/μL (P < .004), and NKG2D(+)CD3(-)CD56(+) T cells/μL (P < .003). Myeloma cell-directed cytotoxicity by the circulating mononuclear cells increased after transplantation (P < .002). When compared to posttransplantation IL-2 therapy alone in this patient population, the addition of cells enriched for NKG2D(+)CD3(+)CD8(+) T cells increased tumor-specific immunity, as demonstrated by enhanced lysis of autologous myeloma cells (P = .02). We postulate that this regimen that increased the number and function of the NKG2D(+)CD3(+)CD8(+) T cells after transplantation may improve clinical outcomes by eliminating residual malignant cells in vivo.