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目的:探讨利用癌症患者自体成纤维细胞作为抗原提呈细胞,诱导抗肿瘤的细胞毒T淋巴细胞(CTL)反应的可能性。方法:制备阳离子脂质体,并包裹大肠癌相关抗原CAHb3。制备自体成纤维细胞、肿瘤细胞和外周血淋巴细胞(PBL)。借助脂质体将CAHb3抗原导入成纤维细胞浆内,采用此细胞抗原周期刺激法,体外诱导抗原特异性CTL反应。制备自体肿瘤的荷瘤鼠模型,并进行过继治疗实验。结果:成功地诱导了抗原特异性CTL反应,获得的CTL在体外对亲本肿瘤细胞有显著的细胞毒活性,而不杀伤异体的抗原靶细胞,其培养上清中IFNγ和TNFα分泌水平增高。结论:大肠癌患者自体成纤维细胞经CAHb3抗原修饰后,可以作为有效的抗原提呈细胞,诱导抗大肠癌的抗原特异性CTL反应。
Objective: To explore the possibility of inducing anti-tumor cytotoxic T lymphocyte (CTL) responses by using autologous fibroblasts from cancer patients as antigen-presenting cells. Methods: Cationic liposomes were prepared and encapsulated with CAHb3, a related antigen of colorectal cancer. Autologous fibroblasts, tumor cells and peripheral blood lymphocytes (PBLs) were prepared. CAHb3 antigen was introduced into the fibroblast cytoplasm by liposomes, and the antigen-specific CTL reaction was induced in vitro using this cell antigen cycle stimulation method. Preparation of tumor-bearing tumor model in mice, and the follow-up treatment experiments. RESULTS: Antigen-specific CTL response was successfully induced. CTL obtained showed significant cytotoxic activity on parental tumor cells in vitro without killing allogeneic antigen target cells, and the secretion level of IFNγ and TNFα increased in the culture supernatant. CONCLUSION: Autologous fibroblasts from patients with colorectal cancer can be used as effective antigen-presenting cells modified by CAHb3 antigen to induce antigen-specific CTL response against colorectal cancer.