Demonstration of dose dependent cytotoxic activity in cancer cells by specific human chorionic gonadotropin monoclonal antibodies.
BACKGROUND
Previous studies in which monoclonal antibodies (MoAbs) were used against different epitopes of human chorionic gonadotropin (hCG) demonstrated the presence of membrane-associated hCG and its subunits by cancer cells of different types and origins and by human embryonic and fetal cells. To elucidate the mechanism of action of a synthetic vaccine against hCG, experiments were conducted to determine the presence or absence of direct dose dependent cytolytic activity by hCG MoAbs, including those elicited by the vaccine.


METHODS
Human adenocarcinoma cells from the uterine cervix (ATCC HeLa CCL 2.0) grown in defined media at 37 degrees C were treated for 2-3 days with different selected doses of each of 12 MoAbs directed against different epitopes of hCG. Three of these MoAbs were against three different epitopes of the synthetic hCGbeta vaccine.


RESULTS
There was a direct dose dependent effect by a MoAb directed against the natural hCGbeta carboxy terminal peptide (CTP), by a MoAb directed against hCGalpha, and by one of the three MoAbs produced by the synthetic hCGbeta-CTP, which is the main component of the World Health Organization (WHO) vaccine being tested for fertility control and for cancer treatment or prevention.


CONCLUSIONS
For the first time (to the authors' knowledge), these results show the existence of hCG MoAbs that have direct dose related cytotoxicity at 37 degrees C and explain the mechanism of action of the WHO anti-hCG vaccine.
Department of Pathology and Laboratory Medicine, Allegheny University of the Health Sciences, MCP-Hahnemann School of Medicine, Allegheny General Hospital Campus, Pittsburgh, Pennsylvania 15212-9986, USA.
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Kalantarov
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Acevedo
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000918:Antibody Specificity; D006063:Chorionic Gonadotropin / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D000939:Epitopes / Q000276:immunology; D006367:HeLa Cells / Q000187:drug effects*; D006801:Humans
D000911:Antibodies, Monoclonal; D006063:Chorionic Gonadotropin; D000939:Epitopes