Adoptive cellular therapy using cells enriched for NKG2D+CD3+CD8+T cells after autologous transplantation for myeloma.
Adoptive cellular therapy using cells enriched for NKG2D+CD3+CD8+T cells after autologous transplantation for myeloma.
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DOI：
10.1016/j.bbmt.2012.08.018
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发表时间：
2013-01
影响因子：
4.3
通讯作者：
Ernstoff, Marc S.
中科院分区：
文献类型：
--
作者：
Meehan, Kenneth R.;Talebian, Laleh;Tosteson, Tor D.;Hill, John M.;Szczepiorkowski, Zbigniew;Sentman, Charles L.;Ernstoff, Marc S.
骨髓瘤患者移植后第15天循环淋巴细胞的数量与生存率的提高相关，但对此起作用的淋巴细胞亚群尚不清楚。NKG 2D是一种自然杀伤（NK）细胞活化受体，介导非MHC限制性和TCR非依赖性细胞裂解。我们的初步结果表明，表达NKG 2D的CD 3 + CD 8 + T细胞可能是一个关键的淋巴细胞群体。一项II期试验检查了在自体移植后第1、2、4和8周输注富含NKG 2D + CD 3 + CD 8 + T细胞的体外扩增细胞的可行性。此外，从移植当天开始，给予低剂量IL-2（6 × 105 IU/m2/天），持续4周。23例患者入组，19例患者可评价。无治疗相关死亡。所有患者均完成了IL-2疗程，并表现出正常的植入。与接受移植但未接受移植后免疫治疗的骨髓瘤患者相比，接受治疗的患者的循环NKG 2D + CD 3 + CD 8 + T细胞数量/μL增加（P < .004），CD 3 + CD 8 + T细胞/μL（P < .04），CD 3 + CD 8 + CD 56 + T细胞/μL（P < .004）和NKG 2D + CD 3 − CD 56 + T细胞/μL（P < .003）。骨髓瘤细胞定向的细胞毒性循环单核细胞移植后增加（P <0.002）。与移植后单独IL-2治疗相比，在该患者人群中，添加NKG 2D + CD 3 + CD 8 + T细胞富集细胞可增加肿瘤特异性免疫，如自体骨髓瘤细胞裂解增强所示（P = .02）。我们推测，这种增加移植后NKG 2D + CD 3 + CD 8 + T细胞数量和功能的方案可能通过消除体内残留的恶性细胞来改善临床结局。
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 × 105 IU/m2/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.
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影响因子：
82.9
作者：
Levine, BL;Bernstein, WB;June, CH
通讯作者：
June, CH
影响因子：
4.4
作者：
Barber, Amorette;Zhang, Tong;Sentman, Charles L.
通讯作者：
Sentman, Charles L.
影响因子：
20.3
作者：
Baker, J;Verneris, MR;Negrin, RS
通讯作者：
Negrin, RS
影响因子：
4.8
作者：
Meehan, KR;Verma, UN;Mazumder, A
通讯作者：
Mazumder, A
影响因子：
4.5
作者：
Meehan, K. R.;Wu, J.;Sentman, C.
通讯作者：
Sentman, C.