Antitumor effect of MCC-465, pegylated liposomal doxorubicin tagged with newly developed monoclonal antibody GAH, in colorectal cancer xenografts

Cancer Sci. 2004 Jul;95(7):608-13. doi: 10.1111/j.1349-7006.2004.tb02495.x.

Abstract

MCC-465 is an immunoliposome-encapsulated doxorubicin. The liposome is tagged with polyethylene glycol and the F(ab')2 of a monoclonal antibody named GAH, a human antibody obtained by the hybridoma technique. The epitope recognized by GAH is not well characterized, but human gastric, colorectal, and mammary cancer cells were GAH-positive, while the normal counterparts were GAH-negative. Pegylated liposome doxorubicin (PLD) and MCC-465 did not show significant antitumor activity against GAH-negative Caco-2 xenografts. On the other hand, MCC-465 exhibited significantly superior antitumor effects against GAH-positive WiDr-Tc and SW837 xenografts, compared with PLD. Immunohistochemistry with GAH revealed that 94% (100 of 106) of surgical specimens of colorectal cancer were GAH-positive. These results warrant a phase I clinical trial of MCC-465 for patients with metastatic colorectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / veterinary
  • Doxorubicin / pharmacology*
  • Humans
  • Hybridomas
  • Liposomes
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Polyethylene Glycols / pharmacology*
  • Transplantation, Heterologous

Substances

  • Antibodies, Monoclonal
  • Liposomes
  • MCC465
  • Polyethylene Glycols
  • Doxorubicin