Radioimmunolocalization of human carcinoma xenografts with B72.3 second generation monoclonal antibodies.
The B72.3 reactive antigen, TAG-72, has been purified and a series of second generation monoclonal antibodies (MAbs), designated CC (colon cancer), have been characterized by a range of in vitro immunological assays. Six CC MAbs (CC11, CC30, CC46, CC49, CC83, and CC92) were chosen for analyses of the in vivo binding to a human colon carcinoma xenograft. All 6 MAbs were previously shown to be distinct from B72.3 and each other by a series of reciprocal competition radio-immunoassays, and all were shown to have a Ka higher than that of B72.3. In this study we demonstrate that all six CC MAbs evaluated are superior to B72.3 in an in vivo tumor targeting model, using human colon carcinoma (LS-174T) xenografts in athymic mice, in terms of both the percentage of the injected dose of radiolabeled MAb delivered per g of tumor and tumor:normal tissue ratios. Differences in the in vivo binding patterns and pharmacokinetics among the CC MAbs are also evaluated. Thus, in light of the fact that B72.3 has been shown to successfully target approximately 75% of primary and metastatic carcinoma lesions in a variety of different carcinoma types in over 300 patients, these studies serve as further evidence to support the clinical evaluation of the second generation CC MAbs, either alone or in combination with B72.3.
Colcher
D
D
Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland 20892.
Minelli
M F
MF
Roselli
M
M
Muraro
R
R
Simpson-Milenic
D
D
Schlom
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000302:isolation & purification; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology; D006801:Humans; D007457:Iodine Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000175:diagnosis* / Q000276:immunology; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D007457:Iodine Radioisotopes