Characterization of anti-self CD8 T-cell responses stimulated by recombinant Listeria monocytogenes expressing the melanoma antigen TRP-2

Bruhn KW; Craft N; Nguyen BD; Yip J; Miller JF

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Characterization of anti-self CD8 T-cell responses stimulated by recombinant Listeria monocytogenes expressing the melanoma antigen TRP-2

机译：表达黑素瘤抗原TRP-2的重组单核细胞增生性李斯特菌刺激的抗自身CD8 T细胞反应的表征

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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.

机译：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情况下递送合适的抗原。我们构建了表达鼠酪氨酸酶相关蛋白2（TRP-2）的单核细胞增生李斯特氏菌（rLM）重组菌株，这是一种在黑素瘤中高度表达的非突变性黑素细胞衍生分化抗原。用该rLM株免疫C57Bl / 6小鼠可有效引发CD8 T细胞，以识别MHC I类限制的TRP-2180-188表位，并在体外肽刺激下表达IFN-γ。在细胞毒性试验中，用TRP-2特异性T细胞在体外裂解了加载了肽的靶细胞，并在功能上保护了用表达TRM-2的rLM免疫和加强免疫的小鼠免受B16黑色素瘤细胞皮下攻击。这些结果鉴定并表征了由表达内源性，未突变的肿瘤抗原的重组单核细胞增生李斯特氏菌诱导的抗“自身” T细胞应答。

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《Vaccine》 |2005年第33期|共10页
作者
Bruhn KW; Craft N; Nguyen BD; Yip J; Miller JF;
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正文语种 eng
中图分类卫生标准、卫生检查、医药管理;
关键词
Animals; Antigens; Neoplasm pharmacology; CD8-Positive T-Lymphocytes drug effects immunology; Intramolecular Oxidoreductases genetics metabolism pharmacology; Listeria monocytogenes genetics; Melanoma; Experimental immunology pathology; Mice; Mice; Inbred C57BL; Recombinant Fusion Proteins genetics immunology pharmacology; Research Support; N.I.H.; Extramural; Research Support; Non-U.S. Gov't; Research Support; U.S. Gov't; P.H.S.;

机译：动物;抗原;肿瘤药理学;CD8阳性T淋巴细胞药物作用免疫学;分子内氧化还原酶遗传学代谢药理学;单核细胞增生李斯特氏菌遗传学;黑素瘤;实验免疫学病理学;小鼠;小鼠;近交C57BL;重组融合蛋白遗传学NIH;校外;研究支持;非美国政府;研究支持;美国政府;P.H.S。;

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专利

1. Characterization of anti-self CD8 T-cell responses stimulated by recombinant Listeria monocytogenes expressing the melanoma antigen TRP-2 [J] . Bruhn KW, Craft N, Nguyen BD, Vaccine . 2005,第33期

机译：表达黑素瘤抗原TRP-2的重组单核细胞增生性李斯特菌刺激的抗自身CD8 T细胞反应的表征
2. CD8+-T-Cell Response to Secreted and Nonsecreted Antigens Delivered by Recombinant Listeria monocytogenes during Secondary Infection [J] . Amy R. Tvinnereim, Sara E. Hamilton, John T. Harty Infection and immunity . 2002,第1期

机译：CD8 + -T细胞对二次感染期间重组李斯特菌重组李斯特菌传递的分泌和非分泌抗原的反应。
3. Tumor-Associated Antigen Expressing Listeria monocytogenes Induces Effective Primary and Memory T-Cell Responses Against Hepatic Colorectal Cancer Metastases [J] . Kelly Olino, Satoshi Wada, Barish H. Edil, Annals of Surgical Oncology . 2012,第s3期

机译：肿瘤相关抗原表达单核细胞增生李斯特菌诱导有效的原发性和记忆性T细胞对肝结直肠癌转移的反应。
4. DYNAMICS OF THE CD8 T-CELL RESPONSEREVEALED BY LISTERIA MONOCYTOGENESINFECTION [C] . John T. Harty International Symposium on Virulence Mechanisms of Bacterial Pathogens . 2007

机译：CD8 T细胞的动态由Histeria单核细胞生殖术反应耐候
5. Applicability of vaccinia virus as cloning and expression vector for bacterial genes: Mice immune responses to vaccinia virus expressing Brucella abortus and Listeria monocytogenes antigens. [D] . Baloglu, Simge. 2006

机译：牛痘病毒作为细菌基因的克隆和表达载体的适用性：小鼠对表达布鲁氏菌流产单核细胞增生李斯特菌抗原的牛痘病毒的免疫反应。
6. Induction of Human Immunodeficiency Virus (HIV)-Specific CD8 T-Cell Responses by Listeria monocytogenes and a Hyperattenuated Listeria Strain Engineered To Express HIV Antigens [O] . Rachel S. Friedman, Fred R. Frankel, Zhan Xu, 2000

机译：单核细胞增生性李斯特菌和经工程改造以表达HIV抗原的超减毒李斯特菌菌株诱导人免疫缺陷病毒（HIV）特异性CD8 T细胞反应。
7. Induction of Human Immunodeficiency Virus (HIV)-Specific CD8 T-Cell Responses by Listeria monocytogenes and a Hyperattenuated Listeria Strain Engineered To Express HIV Antigens [O] . Friedman, Rachel S., Frankel, Fred R., Xu, Zhan, 2000

机译：单核细胞增生性李斯特菌和经工程改造可表达HIV抗原的超减毒李斯特菌菌株诱导人类免疫缺陷病毒（HIV）特异的CD8 T细胞反应。
8. Ligand-Stimulated Signaling Events in Immature CD4+CD8+Thymocytes ExpressingCompetent T-Cell Receptor Complexes [R] . Nakayama, T., Samelson, L. E., Nakayama, Y., 1991

机译：未成熟CD4 + CD8 +胸腺细胞中的配体刺激信号事件表达感受态T细胞受体复合物

Characterization of anti-self CD8 T-cell responses stimulated by recombinant Listeria monocytogenes expressing the melanoma antigen TRP-2

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