Human ovarian cancers specifically bind daunorubicin-OC-125 conjugate: an immunofluorescence study.
This study was designed to test the specific binding to human ovarian serous adenocarcinomas of a drug-antibody conjugate [daunorubicin (DNR-OC-125], made from a new analog (PIPP-DNR) of daunorubicin that chemically links the drug to monoclonal antibodies. We recently reported that the DNR-OC-125 conjugate is selectively toxic in vitro to dividing cell populations of the human ovarian cancer cell lines SK-OV-3 and OVCAR-3 that express the CA-125 antigen [F. Sweet, L. O. Rosik, G. M. Sommers, and J. L. Collins, Gynecol. Oncol. 34, 305-311 (1989)]. In the present study, immunofluorescence data show that the DNR-OC-125 conjugate has high affinity and specificity for proliferating malignant cells from human ovarian tumors. The results demonstrate that the DNR-OC-125 conjugate retains the specific binding to CA-125 antigenic sites characteristic of the OC-125 monoclonal antibody moiety. The DNR-OC-125 conjugate selectively binds to CA-125 antigen-positive ovarian cancerous tissue in both cryostat and paraffin-embedded tissue sections. This is consistent with the earlier in vitro data from dividing populations of two human ovarian cancer cell lines that revealed retention by the DNR-OC-125 conjugate of both the specificity due to OC-125 and the cytotoxicity of daunorubicin. The present immunofluorescence studies in the DNR-OC-125 conjugate is tested on human ovarian serous tumors indicate that the OC-125 monoclonal antibody can indeed serve as a cancer-targeting carrier for daunorubicin and its analogs.
Dezsö
B
B
Department of Pathology, University Medical School of Debrecen, Hungary.
Török
I
I
Rosik
L O
LO
Sweet
F
F
D000911:Antibodies, Monoclonal / Q000378:metabolism; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000032:analysis* / Q000276:immunology; D003536:Cystadenocarcinoma / Q000276:immunology / Q000378:metabolism*; D003630:Daunorubicin / Q000378:metabolism*; D004337:Drug Carriers; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D000922:Immunotoxins / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate; D004337:Drug Carriers; D000922:Immunotoxins; D003630:Daunorubicin