NPFPC Key Laboratory of Contraceptives and Devices, Shanghai Institute of Planned Parenthood Research, Shanghai, 200032, China.
Cancer Immunol Immunother. 2010 Dec;59(12):1771-9. doi: 10.1007/s00262-010-0902-5. Epub 2010 Aug 31.
Human chorionic gonadotropin (hCG) is a membrane-associated protein highly expressed in several types of human cancer cells. The expression in the cancer cells indicates that hCG may be a potential target molecule for cancer immunotherapy. The objective of this study was to develop a novel immunogenic molecule, which can efficiently induce the neutralizing antibody against hCG and which is also suitable for mass production. The immunogenicity of the recombinant single chain chimeric protein of hCGβ-oLHα expressed by yeast was examined. Additionally, the inhibitory effects of the anti-hCGβ-oLHα antibody on the growth of hCG-positive cancer cells were determined. It was found that hCGβ-oLHα yielded high titers of anti-hCG rabbit antibody that could effectively neutralize the bioactivity of hCG. The rabbit anti-hCGβ-oLHα IgG inhibited the proliferation of hCG-expressing human colorectal cancer cells (LS-174, HCT-116, HCT-15 and KM-12) in a dose-dependent manner. Furthermore, an intact anti-tumor vaccine was prepared by conjugating hCGβ-oLHα with tetanus toxoid (TT) and this was used to immunize Balb/c mice bearing hCG-expressing SP2/0 tumor cells. The progression of tumors in these immunized mice was remarkably inhibited. These results suggest that hCGβ-oLHα is a new promising immunogenic molecule for the development of an anti-hCG-based cancer vaccine.
人绒毛膜促性腺激素(hCG)是一种膜相关蛋白,在多种人类癌细胞中高度表达。癌细胞中的表达表明 hCG 可能是癌症免疫治疗的潜在靶分子。本研究的目的是开发一种新型免疫原性分子,该分子能有效地诱导针对 hCG 的中和抗体,并且还适合大规模生产。研究了酵母表达的 hCGβ-oLHα 重组单链嵌合蛋白的免疫原性。此外,还测定了抗-hCGβ-oLHα 抗体对 hCG 阳性癌细胞生长的抑制作用。结果发现,hCGβ-oLHα 产生了针对 hCG 的高滴度兔抗体,可有效中和 hCG 的生物活性。兔抗-hCGβ-oLHα IgG 以剂量依赖性方式抑制 hCG 表达的人结直肠癌细胞(LS-174、HCT-116、HCT-15 和 KM-12)的增殖。此外,通过将 hCGβ-oLHα 与破伤风类毒素(TT)缀合制备了完整的抗肿瘤疫苗,并用于免疫携带 hCG 表达的 SP2/0 肿瘤细胞的 Balb/c 小鼠。这些免疫小鼠的肿瘤进展明显受到抑制。这些结果表明,hCGβ-oLHα 是开发基于 hCG 的癌症疫苗的一种有前途的新型免疫原性分子。