Radioimmunotherapy of human colon cancer xenografts using a dimeric single-chain Fv antibody construct

Gabriela Pavlinkova, Barbara J.M. Booth, Surinder K. Batra, David Colcher

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Abstract

Progress in the use of monoclonal antibodies (MAbs) for the treatment of solid tumors is limited by a number of factors, including poor penetration of the labeled IgG molecule into the tumors, their inability to reach the tumor in sufficient quantities without significant normal tissue toxicity, and the development of a human antimouse antibody response to the injected MAb. One possible way to alter the pharmacology of antibodies is via the use of smaller molecular weight antibody fragments called single-chain Fvs (scFvs). A divalent construct of MAb CC49, CC49 (scFv)2, composed of two noncovalently associated scFvs, was generated and shown to bind a tumor- associated antigen (TAG-72) epitope with a similar binding affinity to that of the murine IgG. The therapeutic potential of this construct after labeling with 131I was examined in athymic mice bearing established s.c. human colon carcinoma (LS-174T) xenografts. Treatment groups (n = 10) received a single dose of 131I-labeled CC49 (scFv)2 (500-2000 μCi) or 131I- labeled CC49 IgG (250 and 500 μCi). The group of mice treated with the lowest dose of 131-(scFv)2 (500 μCi) showed statistically significant prolonged survival, compared with controls (P = 0.036). Complete tumor regression was observed in 20% of mice given 1500 μCi of labeled (scFv)2 and 30 and 60% of mice treated with 250 and 500 μCi of labeled IgG, respectively. In conclusion, the CC49 (scFv)2 construct provides a promising delivery vehicle for therapeutic applications.

Original languageEnglish (US)
Pages (from-to)2613-2619
Number of pages7
JournalClinical Cancer Research
Volume5
Issue number9
StatePublished - Sep 1 1999

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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