Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto, 860-8556, Japan.
Immunol Lett. 2009 Sep 22;126(1-2):67-72. doi: 10.1016/j.imlet.2009.08.001. Epub 2009 Aug 12.
In vivo assay to evaluate anti-cancer immunotherapy at the pre-clinical phase is eagerly needed. We currently established xenotransplantation-based method to analyze in vivo priming of cancer-antigen-specific human cytotoxic T lymphocytes (CTLs). We transplanted human peripheral T cells and analyzed priming of CTLs in NOG mice. Half of the mice engrafted with bulk lymphocytes including CD4(+) T cells died before analysis probably due to xenoreactive graft versus host disease. All of the mice engrafted with purified CD8(+) T cells survived until the analysis, and successful engraftment was observed in 80% of recipient mice. Thus, transfer of purified CD8(+) T cells is sufficient and safer than that of bulk lymphocytes. To add antigenic stimulation to the CD8(+) T cells in vivo, injection of antigenic peptide-loaded and monocyte-derived autologous dendritic cells (DCs) was simultaneously done and repeated 7 days later. The DC-based vaccinization resulted in efficient priming of HLA class I-restricted and MART1, WT1 or CMV peptides-specific CTLs in the recipient mice. This system may be useful to evaluate the stimulation of antigen-specific human CTLs in vivo.
在临床前阶段评估抗癌免疫疗法的体内分析迫切需要。我们目前建立了基于异种移植的方法来分析体内癌症抗原特异性人细胞毒性 T 淋巴细胞（CTL）的启动。我们移植了人外周 T 细胞，并在 NOG 小鼠中分析了 CTL 的启动。一半接受包括 CD4+T 细胞在内的大量淋巴细胞移植的小鼠在分析前因异种反应性移植物抗宿主病而死亡。所有接受纯化 CD8+T 细胞移植的小鼠均存活至分析，并且 80%的受体小鼠中观察到成功移植。因此，与大量淋巴细胞相比，纯化的 CD8+T 细胞的转移既充足又安全。为了在体内对 CD8+T 细胞进行抗原刺激，同时注射负载抗原肽的和单核细胞衍生的自体树突状细胞（DC），并在 7 天后重复进行。基于 DC 的疫苗接种导致受体小鼠中 HLA Ⅰ类限制和 MART1、WT1 或 CMV 肽特异性 CTL 的有效启动。该系统可能有助于评估体内抗原特异性人 CTL 的刺激。
