[Clinical application of monoclonal antibody-drug conjugates in colorectal carcinoma].
Monoclonal antibody, A7, produced from a mouse splenocyte immunized against human colon cancer was used as drug carrier for colon cancer. A7 had not ADCC and ADMC activity but had ACD activity. Anticancer drug, mitomycin C (MMC), and neocarzinostatin (NCS), were covalently bound to A7 to form the conjugates, A7-MMC, and, A7-NCS. In vitro cytotoxic effect of the conjugates on SW1116 was much stronger than that of free MMC or free NCS. The conjugates, A7-NCS, administered in nude mice brought about the highest NCS concentration in tumor, while normal IgG-NCS distributed evenly in all the tissues. The conjugates showed strong antitumor effect on colon cancer transplanted in nude mice. Forty one patients with colorectal cancer including 10 patients with postoperative metastasis were given A7-NCS. The immunoperoxidase and drug concentration studies of the resected specimens revealed that NCS was found to be localized specifically in cancer. There was no serious adverse effect in the patients receiving the conjugate. Of eight patients with postoperative liver metastasis, three showed evidence of tumor reduction on CT scan and three claimed pain relief. The conjugate was of no benefit to the patients with multiple lung metastasis and peritoneal metastasis.
Takahashi
T
T
1st Dept. of Surgery, Kyoto Prefectural University of Medicine.
Sakita
M
M
Yamaguchi
T
T
Kitamura
K
K
Hata
K
K
Noguchi
A
A
D000328:Adult; D000368:Aged; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000473:pathology / Q000628:therapy*; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D016685:Mitomycin; D008937:Mitomycins / Q000627:therapeutic use*; D009368:Neoplasm Transplantation; D012004:Rectal Neoplasms / Q000473:pathology / Q000628:therapy*; D009353:Zinostatin / Q000627:therapeutic use*
D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D008937:Mitomycins; D016685:Mitomycin; D009353:Zinostatin