Experimental and clinical analysis of the characteristics of a chimeric monoclonal antibody, MOv18, reactive with an ovarian cancer-associated antigen.
Monoclonal antibody (Mab) MOv18 preferentially reacts with gynecological carcinomas. We have analyzed the characteristics of murine MOv18 (m-MOv18) and chimeric MOv18 (c-MOv18). We found no differences in affinity and binding to IGROV1 cells between c-MOv18 as IgG and F(ab')2 fragments and m-MOv18. In nude mice bearing IGROV1 xenografts, maximum tumor uptake 6-15 hr after i.v. injection of radiolabeled m-MOv18 IgG, c-MOv18 IgG, c-MOv18 F(ab')2 and a control IgG, 2C7, was 10%, 11%, 3% and 4.5% of the injected dose/g (%ID/g), respectively. M- and c-MOv18 IgG retained this level for several days, while c-MOv18 F(ab')2 and 2C7 cleared rapidly from the tumor. Uptake in normal tissues was low, with the exception of high uptake in kidneys for c-MOv18 F(ab')2. Tumor/blood ratios for c-MOv18 F(ab')2 were sixfold higher than for IgG. Radiation absorbed doses to tumor tissue delivered by 10 microCi iodinated m-MOv18 IgG, c-MOv18 IgG and c-MOv18 F(ab')2 were 39 cGy, 49 cGy and 5 cGy, respectively. A cocktail of 125I-c-MOv18 IgG and 131I-c-MOv18 F(ab')2 injected i.v. into an ovarian cancer patient, localized specifically in the tumor. Ovarian cancer tissue samples obtained 2 days postinjection showed a mean uptake of 1.2 x 10(-3) and 2.7 x 10(-3) %ID/g for c-MOv18 IgG and c-MOv18 F(ab')2, respectively. Results from these in vitro and in vivo experiments indicate that c-MOv18 has promise as a Mab for clinical use.
Molthoff
C F
CF
Free University Hospital, Department of Medical Oncology, Amsterdam, The Netherlands.
Buist
M R
MR
Kenemans
P
P
Pinedo
H M
HM
Boven
E
E
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D000951:Antigens, Neoplasm / Q000276:immunology*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000276:immunology*; D016719:Radioimmunodetection; D011993:Recombinant Fusion Proteins; D014407:Tumor Cells, Cultured / Q000276:immunology
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D007457:Iodine Radioisotopes; D011993:Recombinant Fusion Proteins