Inhibition of tumor growth in vitro and in vivo by a monoclonal antibody against human chorionic gonadotropin beta.
Human chorionic gonadotropin (hCG) beta-subunit (hCGbeta) has been detected in a wide variety of tumors and implicated in tumor maintenance and progression. To better facilitate the investigation of the expression and biological roles of hCGbeta, we generated a set of monoclonal antibodies (mAbs) against hCGbeta by the approach of DNA immunization. All the generated mAbs worked well in detecting native hCGbeta antigen, while some of them were surprisingly found to exhibit potential cytotoxicity to tumor cells in our preliminary experiments. Here, one of those cytotoxic anti-hCGbeta mAb 6H1 was evaluated in detail for its anti-tumor efficacy in vitro and in vivo. 6H1 showed high binding specificity to hCGbeta, which was analyzed by Western blot and ELISA as well as indirect immunofluorescence assay. Treatment with 6H1 inhibited the growth of a panel of hCGbeta-expressing tumor cell lines (HeLa, HL-60, HepG2, SMMC-7721, PC-3) in vitro. Moreover, 6H1 significantly delayed the growth of HeLa-borne tumors in nude mice and prolonged the survival of tumor-bearing mice. The anti-tumor effect of 6H1 was associated with the induction of apoptosis, which was estimated by Hoechst 33258 staining, DNA ladder assay and flow cytometry. Collectively, 6H1 revealed potent anti-tumor activity in vitro and in vivo and therefore may be an effective therapeutic candidate for immuno-intervention of cancers that ectopically express hCGbeta.
Yu
Ning
N
Department of Immunology, Institute for ImmunoBiology, Shanghai Medical College of Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, PR China.
Xu
Wei
W
Jiang
Zhenggang
Z
Cao
Qinghua
Q
Chu
Yiwei
Y
Xiong
Sidong
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D018997:Chorionic Gonadotropin, beta Subunit, Human