Mundhada Shailendra, Shaw Joanne, Mori Shahram, Savary Cherylyn A, Mullen Craig A
Department of Pediatrics, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Leuk Lymphoma. 2005 Apr;46(4):571-80. doi: 10.1080/10428190500032596.
In allogeneic hematopoietic stem cell (HSC) transplantation, graft vs. tumor (GVT) activity contributes to the cancer cure. It is closely associated with graft vs. host disease (GVHD), an immune response initiated by transplanted donor T-cell responses against host minor histocompatibility antigens (mHAgs). GVHD is prevented by T-cell depletion of the donor graft, but T-cell depletion also abrogates curative GVT. We wished to test the hypothesis that cellular tumor vaccines administered after T cell-depleted HSC transplant can induce significant GVT effects, despite the absence of transplanted mature donor T cells. In this investigation, a murine model of major histocompatibility complex (MHC)-matched, mHAg-mismatched allogeneic HSC transplant was studied. T cell-depleted or normal T cell-containing grafts were given to myeloablated recipients. Following reconstitution the recipients were vaccinated with tumor vaccines. GVT responses were measured in vitro by T-cell function assays and flow cytometry, and in vivo by tumor burden or survival. Post-transplant tumor vaccines induced effective anti-tumor responses in recipients of T cell-depleted transplants, producing cytolytic and cytokine responses, reduced tumor burden and prolonged survival. Recipients of T cell-depleted transplants that still have significant thymic function may be suitable subjects for post-transplant vaccine therapy.
在异基因造血干细胞（HSC）移植中，移植物抗肿瘤（GVT）活性有助于治愈癌症。它与移植物抗宿主病（GVHD）密切相关，GVHD是由移植的供体T细胞针对宿主次要组织相容性抗原（mHAgs）的反应引发的免疫反应。通过对供体移植物进行T细胞清除可预防GVHD，但T细胞清除也会消除治愈性的GVT。我们希望验证这样一个假设：在T细胞清除的HSC移植后给予细胞肿瘤疫苗，尽管没有移植成熟的供体T细胞，也能诱导显著的GVT效应。在这项研究中，研究了主要组织相容性复合体（MHC）匹配、mHAg不匹配的异基因HSC移植的小鼠模型。将T细胞清除的或含有正常T细胞的移植物给予接受过骨髓清除的受体。重建后，给受体接种肿瘤疫苗。通过T细胞功能测定和流式细胞术在体外测量GVT反应，并通过肿瘤负荷或生存率在体内测量。移植后肿瘤疫苗在T细胞清除的移植受体中诱导了有效的抗肿瘤反应，产生了细胞溶解和细胞因子反应，降低了肿瘤负荷并延长了生存期。仍具有显著胸腺功能的T细胞清除的移植受体可能是移植后疫苗治疗的合适对象。
