期刊
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
卷 19, 期 1, 页码 129-137出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bbmt.2012.08.018
关键词
Myeloma; NKG2D(+)CD8(+) T cells; Immunotherapy; Ex vivo expansion
资金
- Hitchcock Foundation, Dartmouth Medical School
- Dartmouth-Hitchcock Medical Center
- Leukemia and Lymphoma Society [6061-06]
- Dartmouth College COBRE [5P20RR016437-07, R21 CA112761, R01CA095648]
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 x 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/mu L (P < .004), CD3(+)CD8(+) T cells/mu L (P < .04), CD3(+)CD8(+)CD56(+) T cells/mu L (P < .004), and NKG2D(+)CD3(-)CD56(+) T cells/mu L (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. (C) 2013 American Society for Blood and Marrow Transplantation.
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