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.
Rakestraw
S L
SL
Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ 08855-0909.
Tompkins
R G
RG
Yarmush
M L
ML
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