Bruhn Kevin W, Craft Noah, Nguyen Bidong D, Yip Jimmy, Miller Jeff F
Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095-1747, USA.
Vaccine. 2005 Jul 21;23(33):4263-72. doi: 10.1016/j.vaccine.2005.02.018. Epub 2005 Mar 10.
A potential approach to activate tumor-specific T cells is to use live bacterial vectors to deliver appropriate antigens in a highly immunostimulatory context. We constructed a recombinant strain of Listeria monocytogenes (rLM) expressing murine tyrosinase-related protein-2 (TRP-2), a nonmutated melanocyte-derived differentiation antigen highly expressed in melanomas. Immunization of C57Bl/6 mice with this rLM strain efficiently primed CD8 T cells to recognize the MHC class I-restricted TRP-2180-188 epitope and express IFN-gamma upon in vitro peptide stimulation. Peptide-loaded target cells were lysed in vitro by TRP-2-specific T cells in cytotoxicity assays, and mice immunized and boosted with rLM expressing TRP-2 were functionally protected from subcutaneous challenge with B16 melanoma cells. These results identify and characterize the anti-"self" T-cell responses induced by recombinant L. monocytogenes expressing an endogenous, nonmutated tumor antigen.
一种激活肿瘤特异性T细胞的潜在方法是使用活细菌载体在高度免疫刺激的环境中递送适当的抗原。我们构建了一种表达小鼠酪氨酸酶相关蛋白2（TRP-2）的重组单核细胞增生李斯特菌（rLM）菌株，TRP-2是一种未突变的黑素细胞衍生分化抗原，在黑色素瘤中高度表达。用这种rLM菌株免疫C57Bl/6小鼠可有效启动CD8 T细胞识别MHC I类限制性TRP-2180-188表位，并在体外肽刺激时表达γ干扰素。在细胞毒性试验中，负载肽的靶细胞在体外被TRP-2特异性T细胞裂解，用表达TRP-2的rLM免疫并加强免疫的小鼠在功能上受到保护，免受B16黑色素瘤细胞的皮下攻击。这些结果鉴定并表征了由表达内源性、未突变肿瘤抗原的重组单核细胞增生李斯特菌诱导的抗“自身”T细胞反应。
