Anti-gastrin antibodies raised by gastrimmune inhibit growth of the human colorectal tumour AP5

Susan A. Watson, Dov Michaeli, Steven Grimes, Teresa M. Morris, David Crosbee, Mark Wilkinson, Graham Robinson, John F. R. Robertson, Robert J. C. Steele, Jack D. Hardcastle

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30 Citations (Scopus)

Abstract

The neutralising ability of rabbit anti-gastrin-17 (G17) antiserum raised by Gastrimmune, an immunogen constructed of the N-terminal portion of human G17 conjugated to diptheria toxoid (DT), was evaluated. The anti-serum (denoted anti-G17: DT) was shown to displace 125[I] G17 from the gastrin receptors on AR42J cells. The therapeutic effect of the rabbit anti-G17:DT anti-serum was evaluated on a freshly derived human colorectal cancer cell line, AP5, which was shown to express both gastrin receptors and gastrin immunoreactivity as assessed by immunocytochemistry. Rabbit anti-G17:DT anti-serum was shown to block basal in vitro growth of AP5 cells when used at an antigen binding capacity of 3.75 x 10(-9) M. The same dilution of anti-serum completely reversed growth stimulated by human G17 at concentrations of 1 x 10(-10) and 1 x 10(-9) M but did not inhibit growth at 1 x 10(-8) M G17. When AP5 was grown as a xenograft in nude mice, the sensitivity to the proliferative effect of human G17 was maintained. In addition, the basal growth of AP5 xenografts was significantly reduced by i.v. infusion of rabbit anti-G17:DT anti-serum when compared to treatment with rabbit anti:DT control anti-serum. Thus anti-G17:DT antibodies raised by Gastrimmune may be of clinical value in gastrin-sensitive tumours.

Original languageEnglish
Pages (from-to)233-240
Number of pages8
JournalInternational Journal of Cancer
Volume61
Issue number2
DOIs
Publication statusPublished - 10 Apr 1995

Keywords

  • 3T3 Cells
  • Animals
  • Antibody Formation
  • Cell Division
  • Cell Line
  • Colorectal Neoplasms
  • Diphtheria Toxoid
  • Fasting
  • Gastrins
  • Humans
  • Immunotherapy
  • Immunotoxins
  • Iodine Radioisotopes
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • Pancreas
  • Rabbits
  • Rats
  • Transplantation, Heterologous
  • Tumor Cells, Cultured

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