ANTIGASTRIN ANTIBODIES RAISED BY GASTRIMMUNE INHIBIT GROWTH OF THE HUMAN COLORECTAL TUMOR AP5

The neutralising ability of rabbit anti-gastrin-17 (G17) antiserum rai sed by Gastrimmune, an immunogen constructed of the hi-terminal portio n of human G17 conjugated to diptheria toroid (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 t he rabbit anti-G17:DT anti-serum was evaluated on a freshly derived hu man colorectal cancer cell line, AP5, which was shown to express both gastrin receptors and gastrin immunoreactivity as assessed by immunocy tochemistry. 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 wa s grown as a xenograft in nude mice, the sensitivity to the proliferat ive 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. (C) 1995 Wiley -Liss, Inc.