In vivo fate of monoclonal antibody B72.3 in patients with colorectal cancer.
Radiolabeled B72.3 (anti-TAG-72) has been shown to selectively localize metastatic lesions in 70%-80% of the cases. Serum samples from 27 colorectal carcinoma patients who received iodine-131-(131I) B72.3 by i.v. administration were analyzed. Circulating immunoreactive antibody followed a biphasic clearance pattern. High-performance liquid chromatography (HPLC) and SDS-polyacrylamide gel electrophoresis demonstrated that 131I-B72.3 retained its integrity in the patients' sera. HPLC analysis also demonstrated the presence of immune complexes in the sera of 12 patients; this correlated with elevated levels of circulating TAG-72. Several different HAMA response patterns were detected in the 25 patients' sera that were analyzed; some patients developed HAMA as early as 5-7 days post-MAb injection. Higher doses of administered MAb B72.3 correlated with the development of HAMA (p = 0.007). The presence of elevated levels of TAG-72 in the patients' pre-inoculum serum was shown to correlate with the detection of lesions by gamma scanning. Serum TAG-72 may serve as a criteria for patient selection for immunodiagnostic or immunotherapeutic procedures using MAb B72.3.
Colcher
D
D
Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Milenic
D E
DE
Ferroni
P
P
Carrasquillo
J A
JA
Reynolds
J C
JC
Roselli
M
M
Larson
S M
SM
Schlom
J
J
D000230:Adenocarcinoma / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology / Q000493:pharmacokinetics*; D000936:Antigen-Antibody Complex / Q000097:blood; D000951:Antigens, Neoplasm / Q000097:blood / Q000276:immunology; D002851:Chromatography, High Pressure Liquid; D015179:Colorectal Neoplasms / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006023:Glycoproteins / Q000097:blood / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008875:Middle Aged; D011863:Radioimmunoassay
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000951:Antigens, Neoplasm; D006023:Glycoproteins; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; C047052:tumor-associated antigen 72