Clinical application of monoclonal antibody-drug conjugates for immunotargeting chemotherapy of colorectal carcinoma.
Monoclonal antibody-drug conjugates were applied as a clinical trial for patients who, based on the experimental study, had colorectal cancer. Monoclonal antibody A7, from a mouse splenocyte immunized against human colon cancer, was used as a drug carrier for colon cancer. The anti-cancer drugs mitomycin C (MMC) and neocarzinostatin (NCS) were bound covalently to A7 to form the conjugates A7-MMC and A7-NCS. The in vitro cytotoxic effects of the conjugates on SW1116 cells were stronger than those on free MMC or NCS. The conjugate A7-NCS, when administered to nude mice, brought about the highest NCS tumor concentration, whereas normal immunoglobulin G (IgG)-NCS distributed evenly in all tissues. The conjugates showed a strong antitumor effect on colon cancer transplanted into nude mice. Forty-one patients with colorectal cancer, including ten patients with postoperative metastasis, were given A7-NCS. The immunoperoxidase and drug concentration studies of the resected specimens showed that NCS was localized specifically in cancer. Patients receiving the conjugate did not experience serious adverse effects. Of the eight patients with postoperative liver metastasis, three showed evidence of tumor reduction on computed tomography (CT) scan and three claimed pain relief. The conjugate did not benefit patients with multiple lung metastasis or peritoneal metastasis.
D000328:Adult; D000368:Aged; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D016685:Mitomycin; D008937:Mitomycins / Q000008:administration & dosage*; D009368:Neoplasm Transplantation; D012004:Rectal Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D009353:Zinostatin / Q000008:administration & dosage*
D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D008937:Mitomycins; D016685:Mitomycin; D009353:Zinostatin