The GI-4000 vaccine is built from the tarmogen platform . Tarmogens are heat inactivated yeast which contain overexpressed proteins. In the case of GI-4000 they contain peptides of mutated RAS. The KRAS gene is mutated in 90% of pancreatic cancers. In a phase II trial GI-4000 showed a trend towards improved survival in a subset of pancreatic cancer patients, those with post-operative residual disease .
From biopsies of this patient subset a biomarker companion diagnostic was developed retrospectively by MALDI-TOF mass spectrometry that can identify pancreatic cancer patients as likely to respond to GI-4000 . In theory this could be converted to a next generation sequence based diagnostic and this may become a cheaper option as sequencing costs continue to fall. A phase III trial to confirm or refute the effectiveness of GI-4000 in patients identified as eligible by the companion diagnostic remains to be carried out. The potential for combination with checkpoint inhibitors which theoretically should be highly synergistic with the mechanism of action of GI-4000 are no doubt also under consideration.
- ‘GlobeImmune’s $69M IPO Designed to Build Immunotherapy Pipeline – FierceBiotech’. Accessed 21 March 2016. http://www.fiercebiotech.com/story/globeimmunes-69m-ipo-designed-build-immunotherapy-pipeline/2012-07-03.
- Richards, Donald A., Peter Muscarella, Tanios Bekaii-Saab, Lalan S. Wilfong, Vic Velanovich, Julian Raynov, Patrick J. Flynn, et al. ‘Abstract 5314: A Proteomic Signature Predicts Response to a Therapeutic Vaccine in Pancreas Cancer; Analysis from the GI-4000-02 Trial’. Cancer Research 74, no. 19 Supplement (10 January 2014): 5314–5314. doi:10.1158/1538-7445.AM2014-5314.