Tumors accumulate spontaneous somatic mutations which can give rise to neo-epitopes (neoantigens) recognizable as non-self by T-cells. Advances in next-generation sequencing and bioinformatics make it possible to analyze individual patients' tumor genomes and predict immunogenic mutations, which can be synthesized as short peptides, RNA or DNA for use in personalized cancer vaccines. However, these approaches need optimization for safe and effective induction of anti-tumor T-cell responses. We addressed this challenge by complexing synthetic long peptides comprising predicted tumor neo-epitopes to recombinant Hsc70, creating personalized vaccine candidates, AutoSynVax™ (ASV™), administered with QS-21 Stimulon® adjuvant. The same platform comprising Hsc70 plus synthetic long viral peptides was previously validated in a Phase-2 clinical trial, demonstrating effective T-cell responses and reduced viral load in HSV-2+ subjects. ASV immunization is intended to facilitate antigen processing and presentation of neo-epitopes to T-cells, resulting in robust immune responses. The innate immune modulating properties of the Hsc70 protein as well as that of QS-21 Stimulon adjuvant are also under investigation at the vaccine injection site, in draining lymph node, and in cultures of antigen presenting cell populations exposed to the two agents. Finally, ASV is being explored in combination with various agonistic and antagonistic immune modulating monoclonal antibodies with the aim of increasing the duration of immunological memory and durability of tumor control. With an acceptable safety profile associated with Hsc70 and QS-21 Stimulon exposure in humans and demonstrated preclinical anti-tumor activity of ASV, we are poised to begin a first-in-human clinical trial by the first half of 2017.
Citation Format: Mithun Khattar, Antoine Tanne, Benjamin Morin, Nicholas Wilson, Mohamed Uduman, Justin Zelin, Robert Stein, Mark Exley, John Castle, Daniel L. Levey. Pre-clinical development of a first-in-class fully synthetic heat shock protein-based personalized cancer vaccine [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A028.
- ©2016 American Association for Cancer Research.