Zöller Margot
Department of Tumor Progression and Tumor Defense, German Cancer Research Center, Heidelberg, Germany.
J Immunol. 2003 Dec 15;171(12):6941-53. doi: 10.4049/jimmunol.171.12.6941.
Allogeneic bone marrow cell reconstitution of the nonmyeloablatively conditioned host is supposed to provide an optimized platform for tumor vaccination. We recently showed that an allogeneic T cell-depleted graft was well accepted if the tumor-bearing host was NK depleted. Based on this finding, a vaccination protocol in tumor-bearing, nonmyeloablatively conditioned, allogeneically reconstituted mice was elaborated. Allogeneically reconstituted mice, bearing a renal cell carcinoma, received tumor-primed donor lymph node cells (LNC), which had or had not matured in the allogeneic host. Primed LNC were supported by tumor lysate-pulsed dendritic cells, which were donor or host derived. Optimal responses against the tumor were observed with host-tolerant, tumor-primed LNC in combination with host-derived dendritic cells. High frequencies of tumor-specific proliferating and CTLs were recorded; the survival time of tumor-bearing mice was significantly prolonged, and in >50% of mice the tumor was completely rejected. Notably, severe graft-vs-host disease was observed in reconstituted mice that received tumor-primed LNC, which had not matured in the allogeneic host. However, graft-vs-host was not aggravated after vaccination with tumor-primed, host-tolerant LNC. Thus, the LNC were tolerant toward the host, but not toward the tumor. The finding convincingly demonstrates the feasibility and efficacy of tumor vaccination after allogeneic reconstitution of the nonmyeloablatively conditioned host.
非清髓性预处理宿主的异基因骨髓细胞重建被认为可为肿瘤疫苗接种提供一个优化平台。我们最近发现，如果荷瘤宿主的自然杀伤细胞（NK）被清除，那么异基因T细胞去除的移植物会被很好地接受。基于这一发现，我们制定了一种在荷瘤、非清髓性预处理、异基因重建小鼠中的疫苗接种方案。携带肾细胞癌的异基因重建小鼠接受了在异基因宿主中已经或尚未成熟的经肿瘤致敏的供体淋巴结细胞（LNC）。经肿瘤裂解物脉冲处理的树突状细胞（供体或宿主来源）辅助经致敏的LNC。观察到宿主耐受的、经肿瘤致敏的LNC与宿主来源的树突状细胞联合使用时对肿瘤有最佳反应。记录到高频率的肿瘤特异性增殖细胞和细胞毒性T淋巴细胞（CTL）；荷瘤小鼠的生存时间显著延长，并且超过50%的小鼠肿瘤被完全排斥。值得注意的是，在接受了在异基因宿主中尚未成熟的经肿瘤致敏的LNC的重建小鼠中观察到严重的移植物抗宿主病（GVHD）。然而，用经肿瘤致敏的、宿主耐受的LNC进行疫苗接种后GVHD并未加重。因此，LNC对宿主耐受，但对肿瘤不耐受。这一发现令人信服地证明了非清髓性预处理宿主异基因重建后肿瘤疫苗接种的可行性和有效性。
