Abstract 2886: Primate study of TYG100 a novel rationally-designed recombinant vaccine for pancreatic cancer: Immunogenicity and tolerability in a species-homologous mode
Authors: Broome Paul , Wardle Robert L. , Wang X , Gaier Sonia , Pichler Johannes , Chandler Joyce , Katwa Laxman , Reece Shaun , Laing Peter , Mudde Geert C. , Scott Michael van 
Published: May 2015

Gastrin neutralisation by active immunisation with a DT-conjugated gastrin peptide construct (G17DT) using a mineral oil adjuvant has been shown in several clinical trials to extend median survival in pancreatic cancer patients ineligible or unwilling for chemotherapy[1]. However, survival benefit was highly significant (P &lt;0.003) only in immunological responders to the vaccine (70% of subjects) and correlated with the gastrin neutralising capacity of the induced immune response. The efficacy of a gastrin vaccine in pancreatic cancer could be improved by increasing immune response rates. Injection site reactions limited the number of doses in some patients, thus a less reactogenic vaccine could prove more effective by allowing more doses to be given.

We have developed a novel, rationally designed, recombinant vaccine using the S-TIR™-platform which targets the gastrin immunogen, to CD32-expressing antigen presenting cells, while activating plasmacytoid dendritic cells through its intrinsic adjuvant activity. This new vaccine construct, applied to little gastrin (G17), gives minimal injection site reactions and generates strong gastrin-neutralizing responses. Three doses of 62mcg of the new vaccine, TYG100, were administered to 6 adult cynomolgus monkeys at 0,2 and 4 weeks with bleeds at days 0, 14, 29, 42, 63, 83, 98. All animals responded with detectable ab at day 14, high titres at day 29, peaking at day 42 (titre 1/62,500), to human G17 and gly-G17 with no signs of local or systemic reaction. Haematological and biochemical profiles were unchanged from baseline. Re-immunisation following decay of the antibody levels resulted in a typical anamnestic increase in the response to prior peak levels. Elisa results in this autologous system suggest 2-3 orders of magnitude increase over those achieved with the earlier G17DT immunogen. Inhibition assays showed the antibodies to react equally to both gly-extended and amidated human G17. Use of this novel targetting and adjuvanting system should increase substantially the proportion of immune responders, thus improving survival in pancreatic cancer and providing a considerable advance in gastrin hormone therapy.

1

An International Multicenter Randomized Controlled Trial of G17DT in Patients With Pancreatic Cancer; Gilliam AD, Broome P, et al Pancreas 2012 Apr;41(3):374-9

Citation Format: Paul Broome, Robert L. Wardle, X Wang, Sonia Gaier, Johannes Pichler, Joyce Chandler, Laxman Katwa, Shaun Reece, Peter Laing, Geert C. Mudde, Michael van Scott. Primate study of TYG100 a novel rationally-designed recombinant vaccine for pancreatic cancer: Immunogenicity and tolerability in a species-homologous mode. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2886. doi:10.1158/1538-7445.AM2014-2886