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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Transcription factor Fos-related antigen 1 is an effective target for a breast cancer vaccine.
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Transcription factor Fos-related antigen 1 is an effective target for a breast cancer vaccine.

机译：转录因子Fos相关抗原1是乳腺癌疫苗的有效靶标。

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摘要

Protection against breast cancer was achieved with a DNA vaccine against murine transcription factor Fos-related antigen 1, which is overexpressed in aggressively proliferating D2F2 murine breast carcinoma. Growth of primary s.c. tumor and dissemination of pulmonary metastases was markedly suppressed by this oral DNA vaccine, carried by attenuated Salmonella typhimurium, encoding murine Fos-related antigen 1, fused with mutant polyubiquitin, and cotransformed with secretory murine IL-18. The life span of 60% of vaccinated mice was tripled in the absence of detectable tumor growth after lethal tumor cell challenge. Immunological mechanisms involved activation of T, natural killer, and dendritic cells, as indicated by up-regulation of their activation markers and costimulatory molecules. Markedly increased specific target cell lysis was mediated by both MHC class I-restricted CD8+ T cells and natural killer cells isolated from splenocytes of vaccinated mice, including a significant release of proinflammatory cytokines IFN-gamma and IL-2. Importantly, fluorescence analysis of fibroblast growth factor 2 and tumor cell-induced vessel growth in Matrigel plugs demonstrated marked suppression of angiogenesis only in vaccinated animals. Taken together, this multifunctional DNA vaccine proved effective in protecting against growth and metastases of breast cancer by combining the action of immune effector cells with suppression of tumor angiogenesis.
机译：用抗鼠转录因子Fos相关抗原1的DNA疫苗可实现对乳腺癌的保护，该疫苗在积极增殖的D2F2鼠乳腺癌中过表达。小学的成长该减毒鼠伤寒沙门氏菌携带编码鼠Fos相关抗原1的减毒沙门氏菌携带，与突变型多泛素融合，并与分泌型鼠IL-18共转化，可显着抑制肿瘤和肺转移的扩散。在致死性肿瘤细胞攻击后，在没有可检测到的肿瘤生长的情况下，60％接种的小鼠的寿命增加了两倍。免疫机制涉及T，自然杀伤细胞和树突状细胞的激活，如其激活标记和共刺激分子的上调所表明的。从接种疫苗的小鼠脾细胞分离的MHC I类限制的CD8 + T细胞和自然杀伤细胞介导的特异性靶细胞裂解明显增加，包括促炎性细胞因子IFN-γ和IL-2的大量释放。重要的是，Matrigel塞中成纤维细胞生长因子2的荧光分析和肿瘤细胞诱导的血管生长证明仅在接种动物中显着抑制了血管生成。综上所述，通过结合免疫效应细胞的作用与抑制肿瘤血管生成，这种多功能的DNA疫苗被证明可有效预防乳腺癌的生长和转移。

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