A novel method of conjugation of daunomycin with antibody with a poly-L-glutamic acid derivative as intermediate drug carrier. An anti-alpha-fetoprotein antibody-daunomycin conjugate.
In studies on antitumor antibody-cytotoxic drug conjugates as potential antitumor agents with improved tumor specificity, daunomycin (DM) was first linked to a poly-L-glutamic acid (PLGA) derivative having a single masked thiol group. At the thiol group, DM-linked PLGA was bound to horse anti-rat alpha-fetoprotein (AFP) antibody. The anti-AFP antibody-PLGA-DM conjugate (anti-AFP conjugate, DM/PLGA/Ig molar binding ratio, 7.5/1.2/1.0) retained most of the antigen-binding activity of the parent antibody and was more potent than either unconjugated DM, a conjugate similarity prepared with normal horse immunoglobulin (normal conjugate), or an unconjugated mixture of anti-AFP antibody and DM in an in vitro cytotoxicity assay against the AFP-producing rat ascites hepatoma cell line AH66. Anti-AFP conjugate tended to be less cytotoxic than DM against the AFP-nonproducing rat ascites hepatoma AH272 cells, and in this case there was no difference between the cytotoxicities of anti-AFP conjugate and of normal conjugate.
D000818:Animals; D000906:Antibodies / Q000138:chemical synthesis* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003630:Daunorubicin / Q000138:chemical synthesis* / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical; D007106:Immune Sera; D007202:Indicators and Reagents; D008114:Liver Neoplasms, Experimental / Q000473:pathology; D051381:Rats; D013056:Spectrophotometry, Ultraviolet; D000509:alpha-Fetoproteins
D000906:Antibodies; D007106:Immune Sera; D007202:Indicators and Reagents; D000509:alpha-Fetoproteins; C043914:anti-alpha-fetoprotein antibody-daunomycin conjugate; D003630:Daunorubicin