ERADICATION OF LARGE COLON-TUMOR XENOGRAFTS BY TARGETED DELIVERY OF MAYTANSINOIDS

The maytansinoid drug DMI is 100- to 1000-fold more cytotoxic than ant icancer drugs that are currently in clinical use. The immunoconjugate C242-DM1 was prepared by conjugating DMI to the monoclonal antibody C2 42, which recognizes a mucin-type glycoprotein expressed to various ex tents by human colorectal cancers, C242-DM1 was found to be highly cyt otoxic toward cultured colon cancer cells in an antigen-specific manne r and showed remarkable antitumor efficacy in vivo. C242-DM1 cured mic e bearing subcutaneous COLO 205 human colon tumor xenografts (tumor si ze at time of treatment 65-130 mm(3)), at doses that shelved very litt le toxicity and were well below the maximum tolerated dose. C242-DM1 c ould even effect complete regressions or cures in animals with large ( 260- to 500-mm(3)) COLO 205 tumor xenografts. Further, C242-DM1 induce d complete regressions of subcutaneous LoVo and HT-29 colon tumor xeno grafts that express the target antigen in a heterogeneous manner, C242 -DM1 represents a new generation of immunoconjugates that may yet fulf ill the promise of effective cancer therapy through antibody targeting of cytotoxic agents.