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Indirect immunotargeting of CIS‐PT to human epidermoid carcinoma KB using the avidin‐biotin system
Author(s) -
Schechter B.,
Ar R.,
Wilchek M.,
Schlessinger J.,
Hurwitz E.,
AboudPirak E.,
Sela M.
Publication year - 1991
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.2910480203
Subject(s) - avidin , biotin , monoclonal antibody , epidermoid carcinoma , microbiology and biotechnology , epidermal growth factor , antibody , conjugate , chemistry , biology , carcinoma , medicine , receptor , biochemistry , immunology , pathology , mathematical analysis , mathematics
Cis‐diamminedichloroplatinum (II) (cis‐Pt) complexed to a carboxymethyl dextran‐avidin conjugate was targeted to biotin‐monoclonal antibody 108 (b‐MAb108). This MAb recognizes the extracellular domain of the epidermal growth factor receptor (EGF‐R) on human epidermoid carcinoma (KB) cells over‐expressing EGF‐R. Cis‐Pt‐carboxymethyl‐dextran‐avidin (Pt‐dex‐Av) containing 60–90 M cis‐Pt/M avidin was administered 24 hr following b‐MAb108 containing 3–5 M biotin/ M MAb. This treatment was potentially more effective in suppressing the growth of established KB tumor xenografts, or in inhibiting the development of lung metastases in nude mice, than free MAb 108, free drug or MAb 108 followed by drug. Replacing b‐MAb108 by unbiotinylated antibody or by b‐MAb of a different specificity also yielded lower suppressive effects. The sequential administration of Pt‐dex‐Av following b‐MAb was more effective than Introduction, of the Pt‐dex‐Av when already complexed to b‐MAb 108. The results presented in this preliminary investigation suggest that Pt‐dex‐Av is specifically removed from the circulation by b‐MAb 108 concentrated at the tumor site.