| Abstract: | K18 is a new drug produced by a combination of Melphalan and human immunoglobulin. K18 produced an inhibitory effect on the proliferation of human gastric and colon cancer transplanted in to nude mice. Also, combination effects of K18 with MMC and 5-FU were recognized in the same system. In a study of distribution after K18 administration, the accumulation and retention of this drug in the tumor region were observed. In the case of Melphalan administration, these phenomena were not observed. The antitumor activity of tumor homogenate was evaluated using a colony-forming assay with KB cells. As to the Melphalan-treated group, a four-hour homogenate reduced the number of colonies but a 48-h one did not. In the K18-treated group, the four-hour homogenate decreased the number slightly and the decrease became obvious with 48-h homogenate. In cell cycle analysis using K18 or Melphalan administration, gathering of S-phase cells was observed, but these changes appeared later with K18 than with Melphalan. This result showed that the effect of K18 was produced by the alkylating activity of Melphalan which was combined with immunoglobulin. For clinical application, K18 was administered to cancer patients at a dose of 60-90 mg every day. Two cases of good response were achieved. No side effect was observed. This remarkable efficacy and low degree of side effects in clinical application is probably due to the higher affinity and accumulation of K18 in the tumor region. K18 is a useful new drug for clinical application alone, or in combination with other chemotherapeutic drugs. |
