Antibody-targeted photolysis: in vitro studies with Sn(IV) chlorin e6 covalently bound to monoclonal antibodies using a modified dextran carrier.
A monoclonal antibody-dextran-Sn(IV) chlorin e6 immunoconjugate was prepared by a technique involving the site-specific covalent modification of the monoclonal antibody oligosaccharide moiety. Dextran carriers were synthesized with a single chain-terminal hydrazide group, which was used as the coupling point between the carrier and the monoclonal antibody carbohydrate. Selective in vitro photolysis of SK-MEL-2 human malignant melanoma cells was accomplished using several conjugates prepared from anti-melanoma 2.1 (chromophore:antibody molar ratios, 6.8 and 11.2). Phototoxicity, as measured by clonogenic assay, was dependent on the delivered dose of 634-nm light and was observed only for conjugates that bound SK-MEL-2 cells. As judged by competitive inhibition radioimmunoassay, conjugates prepared in this fashion showed excellent retention of antigen binding activity relative to the unmodified antibody.
Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ 08855-0909.
S L
SL
Rakestraw
R G
RG
Tompkins
M L
ML
Yarmush
D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D055598:Chemical Phenomena; D002621:Chemistry; D003911:Dextrans; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage*; D066298:In Vitro Techniques; D010777:Photochemistry; D011166:Porphyrins / Q000008:administration & dosage*; D014001:Tin; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D003911:Dextrans; D000922:Immunotoxins; D011166:Porphyrins; C006969:chlorin; D014001:Tin