Evaluation of the immunogenicity of a single chain chimeric peptide composed of hCGβ and oLHα for inhibition of the growth of hCGβ-expressing cancer cells

摘要

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.