Eradication of large colon tumor xenografts by targeted delivery of maytansinoids.

Abstract:

:The maytansinoid drug DM1 is 100- to 1000-fold more cytotoxic than anticancer drugs that are currently in clinical use. The immunoconjugate C242-DM1 was prepared by conjugating DM1 to the monoclonal antibody C242, which recognizes a mucin-type glycoprotein expressed to various extents by human colorectal cancers. C242-DM1 was found to be highly cytotoxic toward cultured colon cancer cells in an antigen-specific manner and showed remarkable antitumor efficacy in vivo. C242-DM1 cured mice bearing subcutaneous COLO 205 human colon tumor xenografts (tumor size at time of treatment 65-130 mm3), at doses that showed very little toxicity and were well below the maximum tolerated dose. C242-DM1 could even effect complete regressions or cures in animals with large (260- to 500-mm3) COLO 205 tumor xenografts. Further, C242-DM1 induced complete regressions of subcutaneous LoVo and HT-29 colon tumor xenografts that express the target antigen in a heterogeneous manner. C242-DM1 represents a new generation of immunoconjugates that may yet fulfill the promise of effective cancer therapy through antibody targeting of cytotoxic agents.

authors

Liu C,Tadayoni BM,Bourret LA,Mattocks KM,Derr SM,Widdison WC,Kedersha NL,Ariniello PD,Goldmacher VS,Lambert JM,Blättler WA,Chari RV

doi

10.1073/pnas.93.16.8618

subject

Has Abstract

pub_date

1996-08-06 00:00:00

pages

8618-23

issue

16

eissn

0027-8424

issn

1091-6490

journal_volume

93

pub_type

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