CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Novel vaccination strategies based on optimal stimulation of CD4(+) T helper cells for the treatment of oral squamous cell carcinoma.
Novel vaccination strategies based on optimal stimulation of CD4(+) T helper cells for the treatment of oral squamous cell carcinoma.
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口腔鳞状细胞癌(OSCC)是口腔最常见的恶性肿瘤。尽管近年来口腔癌治疗领域取得了进展,包括免疫治疗方法的引入,但5年生存率仍稳定评估在50%左右。
因此,迫切需要新的治疗策略。在表征三种人OSCC细胞系(CAL-27、SCC-25和SCC-4)和一种小鼠OSCC细胞系(MOC2)的免疫表型,显示其与切除的患者肿瘤具有相似性之后,我们首次探索了一种实验性临床前治疗性疫苗模型,该模型使用稳定表达CIITA基因转染后MHC II类抗原的小鼠OSCC MOC2细胞系(MOC2-CIITA)。注射MOC2-CIITA的小鼠排斥或强烈延缓肿瘤生长;更重要的是,完全排斥MOC2-CIITA肿瘤的疫苗接种动物显示出抗肿瘤免疫记忆,可保护其免受亲本MOC2肿瘤细胞的攻击。
进一步的过继性细胞转移或体内细胞清除实验表明,CD4+和CD8+T淋巴细胞在肿瘤排斥中均发挥基础性作用。这种前所未有的口腔癌方法为未来将新型免疫治疗策略转化至人类用于治疗该肿瘤开辟了道路。
Oral Squamous Cell Carcinoma (OSCC) is the most common malignant tumor of the oral cavity. Despite recent advances in the field of oral cancer therapy, including the introduction of immunotherapeutic approaches, the 5-year survival rate remains steadily assessed around 50%.
Thus, there is an urgent need for new therapeutic strategies. After the characterization of the immune phenotype of three human OSCC cell lines (CAL-27, SCC-25, and SCC-4) and one mouse OSCC cell line (MOC2) showing their similarities to resected patient tumors, we explored for the first time an experimental preclinical model of therapeutic vaccination with mouse OSCC MOC2 cell line stably expressing MHC class II antigens after CIITA gene transfection (MOC2-CIITA).
Mice injected with MOC2-CIITA reject or strongly retard tumor growth; more importantly, vaccinated animals that fully reject MOC2-CIITA tumors display anti-tumor immunological memory protective against challenge with parental MOC2 tumor cells.
Further experiments of adoptive cell transfer or in vivo cell depletion show that both CD4 + and CD8 + T lymphocytes prove fundamental in tumor rejection. This unprecedented approach for oral cancer opens the way for possible future translation of novel immunotherapeutic strategies to the human setting for the treatment of this tumor.
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