GI-4000 in KRAS mutant cancers

Abstract

Introduction: Cancer develops mainly as a result of accumulating mutations in genes controlling cell growth regulation. RAS is one of the most commonly mutated genes in cancer. While agents targeting the signaling aspects of RAS have met with some success, resistance to therapy remains a major issue. Another focus of drug development has been to harness the immune system to target cells harboring mutated proteins, which can appear ‘foreign’ to the immune system. It has been observed that cancer is able to avoid regular immune surveillance through local and systemic mechanisms leading to immune tolerance. One potential way of breaking immune tolerance is through vaccine therapy.

Areas covered: The authors review the current but limited available literature on KRAS vaccine therapy. The research reviewed was identified from PubMed and presentations from national oncology meetings related to KRAS vaccines in general and GI-4000 series specifically.

Expert opinion: While targeting KRAS has proven difficulties, developing novel vaccine approaches such as ‘tarmogens’ appear to be safe with early efficacy in subset of patients with KRAS mutations. However, further research is crucial to identify this group of patients and develop biomarkers.

Keywords::

• cancer
• immunotherapy
• KRAS mutation
• vaccine

Acknowledgments

The authors would like to acknowledge and thank TC Rodell, for providing Figure 1, explaining GI-4000 mechanism of action, which is property of GlobeImmune, Inc.

Notes