Preclinical assessment of anti-cancer drugs by using RP215 monoclonal antibody

Abstract

RP215 monoclonal antibody was originally generated against OC-3-VGH ovarian cancer cells. It was shown to recognize specifically a carbohydrate-associated epitope(s) of cancer cell-expressed immunoglobulin heavy chains designated as CA215. Previous studies suggest that CA215 is expressed by all human cancer cell lines and tissues in both membrane bound and secreted forms. It may be an ideal target for therapeutic treatments of human cancers with humanized RP215-related antibodies. Based on the results of large scale immunohistochemical studies (50-100 cases each), the following types of cancers revealed high percentage(s) of positive staining with RP215: esophagus (76%), stomach (50%), colon (44%), ovary (64%), breast (32%), lung (31%), cervix (84%) and endometrium (78%). Nude mouse experiments were performed to determine if RP215 has any inhibitory effect on the growth of cancer cells in vivo. Following injections of a single dose (10 mg/kg) of I131-labeled RP215 (specific activity, 12.5 μCi/mg), the tumor size (OC-3-VGH ovarian cancer cells) was reduced to 30% of the untreated control within two weeks. By injecting the same dose, the unlabeled RP215 also reduced the tumor size to 50% of the control during the same period. The antibody treatments were found to have little effect on the body weight as well as apparent toxicity of these animals. To proceed with clinical trial studies of RP215-based anti-cancer drugs, chimeric form of this monoclonal antibody was generated and characterized. Through our effort, the "proof of concept" of anti-cancer drugs development was clearly established for the next stages of clinical trial studies.