McCabe B J, Irvine K R, Nishimura M I, Yang J C, Spiess P J, Shulman E P, Rosenberg S A, Restifo N P
Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892, USA.
Cancer Res. 1995 Apr 15;55(8):1741-7.
Anticancer vaccine strategies can now target intracellular antigens that are involved in the process of malignant transformation, such as oncogene products or mutated tumor suppressor genes. Fragments of these antigens, generally 8-10 amino acids in length and complexed with MHC class I molecules, can be recognized by CD8+ T lymphocytes (TCD8+). To explore the possibility of using a genetically encoded, minimally sized fragment of an intracellular antigen as an immunogen, we constructed a recombinant vaccinia virus encoding an 8-residue peptide derived from chicken ovalbumin that is known to associate with the mouse H-2Kb molecule. Compared to standard methods of immunization, recombinant molecule. Compared to standard methods of immunization, recombinant vaccinia virus expressing the minimal determinant as well as full length ovalbumin were the only approaches that elicited specific primary lytic responses in C57BL/6 mice against E.G7OVA, a transfectant of the murine thymoma EL4 containing the ovalbumin gene. Stimulating these effectors in vitro with OVA257-264 peptide induced H-2Kb-restricted TCD8+ that not only lysed but also specifically secreted IFN-gamma in response to an antigen. Furthermore, when transferred adoptively, these anti-OVA257-264 TCD8+ cells significantly reduced the growth of established ovalbumin-transfected tumors in a pulmonary metastasis model system. Synthetic transfected tumors in a pulmonary metastasis model system. Synthetic oligonucleotides encoding minimal antigenic determinants within expression constructs may be a useful approach for treatment of neoplastic disease, thus avoiding the potential hazards of immunizing with full-length cDNAs that are potentially oncogenic.
抗癌疫苗策略现在可以靶向参与恶性转化过程的细胞内抗原，例如癌基因产物或突变的肿瘤抑制基因。这些抗原的片段通常长度为8 - 10个氨基酸，并与MHC I类分子复合，可被CD8 + T淋巴细胞（TCD8 +）识别。为了探索使用细胞内抗原的基因编码的最小尺寸片段作为免疫原的可能性，我们构建了一种重组痘苗病毒，其编码源自鸡卵清蛋白的8个残基的肽，已知该肽与小鼠H - 2Kb分子相关联。与标准免疫方法相比，重组分子。与标准免疫方法相比，表达最小决定簇以及全长卵清蛋白的重组痘苗病毒是仅有的在C57BL / 6小鼠中引发针对E.G7OVA（一种含有卵清蛋白基因的鼠胸腺瘤EL4转染子）的特异性初次裂解反应的方法。用OVA257 - 264肽在体外刺激这些效应细胞可诱导H - 2Kb限制的TCD8 +，其不仅裂解而且还响应抗原特异性分泌IFN - γ。此外，当进行过继转移时，这些抗OVA257 - 264 TCD8 +细胞在肺转移模型系统中显著降低了已建立的卵清蛋白转染肿瘤的生长。肺转移模型系统中的合成转染肿瘤。在表达构建体中编码最小抗原决定簇的合成寡核苷酸可能是治疗肿瘤疾病的一种有用方法，从而避免了用可能致癌的全长cDNA进行免疫的潜在危害。
