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Article
Eradication of large colon tumor xenografts by targeted delivery of maytansinoids
Women’s Health Research Faculty Publications
  • Changnian Liu, ImmunoGen, Inc.
  • B. Mitra Tadayoni, ImmunoGen, Inc.
  • Lizabeth A. Bourret, ImmunoGen, Inc.
  • Kristin M Mattocks, University of Massachusetts Medical School Worcester
  • Susan M. Derr, ImmunoGen, Inc.
  • Wayne C. Widdison, ImmunoGen, Inc.
  • Nancy L. Kedersha, ImmunoGen, Inc.
  • Pamela D Ariniello, ImmunoGen, Inc.
  • Victor S. Goldmacher, ImmunoGen, Inc.
  • John M. Lambert, ImmunoGen, Inc.
  • Walter A. Blattler, ImmunoGen, Inc.
  • Ravi V.J. Chari
UMMS Affiliation
Department of Quantitative Health Sciences
Date
8-6-1996
Document Type
Article
Subjects
Animals; Antibiotics, Antineoplastic; Antibodies, Monoclonal; Antibodies, Neoplasm; Colorectal Neoplasms; Humans; Immunotoxins; Maytansine; Mice; Mice, SCID; Neoplasm Transplantation; Transplantation, Heterologous; Tumor Cells, Cultured
Disciplines
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.
Rights and Permissions
Citation: Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8618-23.
Comments

At time of publication Kristin Mattocks was not yet affiliated with the University of Massachusetts Medical School.

Related Resources
Link to Article in PubMed
PubMed ID
8710920
Citation Information
Changnian Liu, B. Mitra Tadayoni, Lizabeth A. Bourret, Kristin M Mattocks, et al.. "Eradication of large colon tumor xenografts by targeted delivery of maytansinoids" Vol. 93 Iss. 16 (1996) ISSN: 0027-8424 (Linking)
Available at: http://works.bepress.com/kristin_mattocks/32/