[Missile therapy using monoclonal antibody drug conjugates in colorectal carcinoma]

Abstract

For targeting chemotherapy of colorectal carcinoma, mitomycin C (MMC) and neocarzinostatin (NCS) were covalently bound to monoclonal antibody A7 which is highly specific to human colon cancer. The in vitro cytotoxic effects of the conjugates A7-MMC and A7-NCS on SW1116 were 77 times and 4 times stronger than those of the free MMC and free NCS, respectively. An in vivo study in nude mice bearing human colon carcinoma revealed that monoclonal antibody A7 alone had no effect, and that A7-MMC and A7-NCS had greater inhibitory effects than the free MMC and NCS, respectively. Thirty-five patients with carcinoma of the colon and rectum including 6 with postoperative liver metastasis, one with postoperative lung metastasis and one with postoperative peritoneal metastasis, were given the A7-NCS conjugate consisting of between 15 and 90 mg of antibody and between 1,000 and 6,000 units of NCS. Immunoperoxidase study of resected specimens revealed selective localization of NCS in the cancer cells. The conjugate had no serious adverse effects. Five of the six patients with postoperative liver metastasis responded favorably to the conjugate, showing a decrease in tumor size on CT scan or relief of pain. The conjugate was of no benefit to patients with multiple lung metastasis or peritoneal metastasis. The effect on other patients with surgically resected carcinoma remains to be determined by a follow-up study.