[Chemical modification of anti-cancer drugs to increase their affinity to tumor antigens].
In order to increase the selective localization of anti-cancer drugs to the target tumor cells, polyclonal or monoclonal anti alpha-fetoprotein antibody (aAFP) was conjugated with anti-cancer drugs such as daunomycin (DM), adriamycin (AM) and mitomycin C (MMC) by chemical modification. Dextran (Dex) or poly L-glutamic acid (PLGA) was used to bind aAFP with DM (AM) as an intermediate drug carrier. For the conjugation of aAFP with MMC, a direct binding method through the aziridine ring of the activated MMC derivative or an indirect binding method through serum albumin as an intermediate drug carrier was employed. These conjugates caused greater inhibition of both in vitro and in vivo tumor growth of AFP-producing target tumor cells than did a mixture of aAFP and anti-cancer drugs or a simular conjugate of these drugs with normal horse immunoglobulin. AFP has high affinity to unsaturated fatty acids (UFA) such as arachidonic acid (C20:4) and so on. The antitumor effect of UFA-DM conjugate was also assessed using AFP-producing rat ascites hepatoma cells. It was found that UFA-DM conjugated showed highly selective cytocidal effects against the hepatoma cells.
Tsukada
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D003630:Daunorubicin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D016685:Mitomycin; D008937:Mitomycins / Q000008:administration & dosage; D009368:Neoplasm Transplantation; D051381:Rats; D000509:alpha-Fetoproteins / Q000096:biosynthesis / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D008937:Mitomycins; D000509:alpha-Fetoproteins; D016685:Mitomycin; D004317:Doxorubicin; D003630:Daunorubicin