抄録
Monoclonal antibody A7, from a mouse splenocyte immunized against human colon cancer, was used as a drug carrier for colon cancer. Neocarzinostatin(NCS)was bound covalently to A7 to form A7-NCS. The A7-NCS, which exhibited a strong in vitro and in vivo antitumor activity, was applied as a clinical trial for forty-one patients with colorectal cancer. Of the eight patients with liver metastasis, five showed some improvement such as tumor reduction on computed tomography and pain relief. Patients recieving A7-NCS did not experience serious adverse effects. Mitomycin C-dextran conjugate with anionic charge(MMC-Dan)was bound to A7 in order to bind large amount of MMC. Amino groups-introduced MMC-Dan was linked to A7 using SPDP. The molar binding ratio(IgG : dextran : MMC)in the conjugate(A7-MMCD)was estimated to be 1 : 1.2 : 40. Under physiological conditions, MMC was released with a half life of about 29 hours. A competitive binding assay revealed that the A7-MMCD retained almost full antibody activity. The in vitro cytotoxic effect on SW1116 cells was 10 times stronger than MMC-Dan. 111In labeled A7-MMCD accumulated in SW1116 about 5 times greater degree than in sarcoma 180 in mice. The A7-MMCD showed a strong antitumor effect on colon cancer transplanted into nude mice.
