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.