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Biodistribution and histological localization of anti‐human colon cancer monoclonal antibody (MAb) 1A3: The influence of administered MAB dose on tumor uptake
Author(s) -
Fenwick J. R.,
Philpott G. W.,
Connett J. M.
Publication year - 1989
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910440614
Subject(s) - biodistribution , monoclonal antibody , antigen , population , antibody , chemistry , microbiology and biotechnology , epitope , biology , immunology , medicine , in vitro , biochemistry , environmental health
Abstract Using a murine monoclonal antibody MAb 1A3, which binds to a lipid antigen found enriched in human colon cancer, and MOPC‐21 antibody, as a non‐specific control, we examined the effect of increasing doses of 125 l‐labelled MAbs (5μg to 2,000μg) on tumor localization. Biodistribution studies in hamsters with small GW‐39 human colon carcinoma tumors [0.44g ± 0.014 (SEM)] demonstrated functional saturation of antigen binding sites in tumors when large doses of MAb 1A3 were used. The percentage injected dose bound per gram of tumor (ID/g tumor) remained constant for doses of intact MAb 1A3 > 100μg but decreased with doses > 100μg, suggesting that a population of antigen binding sites had been saturated. While the percentage ID/g tumor decreased for doses of MAb 1A3 > 100μg, the absolute amount specifically bound/ g tumor increased (up to the 1,000μg dose), suggesting that another population of less accessible 1A3 antigen could continue to bind MAb 1A3. In contrast, MOPC demonstrated a relatively constant percentage ID/g of tumor (2.26% ± 0.11) throughout the dose range which was 2–3 times lower than MAb 1A3 (6.8% ± 0.14) at plateau doses (5–100μg). These data suggested that specific saturation of tumor binding sites was a biphasic phenomenon. Blood and normal tissues did not show binding kinetics suggesting saturation. Results of dose response experiments using MAb 1A3 F(ab′) 2 fragments (5μg to 1,000μg) closely paralleled those obtained with intact MAb 1A3, but with lower percentages of ID/g tumor, blood and non‐tumor tissues as in previous studies with MAb 1A3 and other MAb F(ab′) 2 fragments. Histological examinations demonstrated that non‐specific binding of MOPC or MAb 1A3 to tumor or normal tissues was of such low affinity as to be largely undetected after histological procedures. In contrast, MAb 1A3 (but not MOPC) showed specific cell‐binding patterns to tumor but not normal tissues at all doses.