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以人绒毛膜促性腺激素β亚基(βhCG)的羧基端109~118的6段串联重复表位为靶点、热休克蛋白65(HSP65)为载体,设计一种新型的蛋白疫苗HSP65-X6-βhCGCTP37,探讨其能否抑制小鼠前列腺癌,并且对其抗肿瘤的作用机理进行部分探讨。以制备的HSP65-X6-βhCGCTP37免疫C57BL/6小鼠,分别检测体液免疫应答和细胞免疫应答。通过ELISA法,从血清中检测到高滴度的抗βhCGIgG类抗体。Western blot实验证明小鼠血清中的抗体能够特异性识别βhCG表位。淋巴细胞增殖实验的结果显示,HSP65-X6-βhCGCTP37的免疫能够有效的刺激脾淋巴细胞的增殖。预防性实验的结果显示,HSP65-X6-βhCGCTP37激发的免疫应答对于RM-1肿瘤攻击起到有效的保护作用,与PBS阴性对照组比较,平均肿瘤重显著降低(P<0.05)。同时有效地减少了小鼠的肺转移(P<0.01);抑制了小鼠皮内肿瘤模型中的血管新生(P<0.01)。HSP65-X6-βhCGCTP37蛋白疫苗能有效地抑制小鼠前列腺癌的生长。
A novel protein vaccine, HSP65-X6, was designed by targeting the 6-segment tandem repeat epitopes at the carboxy-terminal of human chorionic gonadotropin β subunit (βhCG) and heat shock protein 65 (HSP65) -βhCGCTP37 to explore whether it can inhibit the prostate cancer in mice, and its mechanism of anti-tumor part of the study. C57BL / 6 mice were immunized with the prepared HSP65-X6-βhCGCTP37 to detect the humoral immune response and the cellular immune response, respectively. High-titer anti-βhCGIgG-like antibodies were detected from the serum by ELISA. Western blot showed that antibodies in mouse sera specifically recognized the βhCG epitope. The results of lymphocyte proliferation experiments showed that the immunization of HSP65-X6-βhCGCTP37 can effectively stimulate the proliferation of spleen lymphocytes. The results of the preventive experiment showed that the immune response stimulated by HSP65-X6-βhCGCTP37 effectively protected the RM-1 tumor from attack, and the average tumor weight was significantly lower than that of the PBS-negative control group (P <0.05). At the same time, the lung metastasis of mice was effectively reduced (P <0.01). Angiogenesis was inhibited in mouse intradermal tumor model (P <0.01). HSP65-X6-βhCGCTP37 protein vaccine can effectively inhibit the growth of mouse prostate cancer.