Genetic instability is a hallmark of cancer and, consequently, each cancer patient's tumor genome (i.e., the DNA of the tumor cell) is different from their normal cells. This DNA difference leads to the creation of new protein antigens that are specific to tumor cells. These new antigens, known as tumor-specific neo-antigens (TSNAs), can be recognized and targeted by the immune system. This inherent vulnerability of tumor cells is being exploited at Gritstone by identifying a patient's unique set of tumor antigens and deploying them in a therapeutic immunization strategy. Current public approaches to TSNA prediction from sequence data alone lack specificity and sensitivity.
To build a best-in-class TSNA prediction model, large numbers of human tumors were collected (initial focus on NSCLC) and characterized by next-generation DNA sequencing and RNA analysis, together with HLA immuno-peptidomics to measure presented peptides. These data were used to build a neural network-based TSNA prediction model that performs with high positive predictive value and offers broad HLA allelic coverage. The selected TSNA will be delivered in the context of a potent personalized cancer vaccine. The proximal goal of a highly potent TSNA specific cancer vaccine is the induction of hi-titer, polyfunctional and durable CD4+ and CD8+ T-cell responses. This has been demonstrated in humans with viral vector based vaccines such as replication deficient adenoviral vectors delivering viral antigens.
Gritstone is pairing an adenoviral prime vaccination with an RNA based boost vaccination to keep the TSNA specific T-cells at high titers long term. The personalized vaccine is delivered in combination with immune checkpoint blockade, to keep TSNA-induced T-cells active in the immunosuppressive tumor microenvironment. Data will be presented supporting this novel approach to TSNA identification through integrated tumor tissue analysis and deep learning, in the context of the potential impact for the development of personalized cancer immunotherapy.
Karin Jooss serves as Chief Scientific Officer of Gritstone Oncology. Dr. Jooss joined Gritstone from Pfizer, where she served as head of Cancer Immunotherapeutics within the Vaccine Immunotherapeutics department for seven years. While at Pfizer, she built and led immuno-oncology teams, was a member of the Vaccine Immunotherapeutics leadership team and served as the head of the Immunophamacology team. Her duties included overseeing the assessment of all cancer vaccine in-licensing opportunities, and developing and launching Pfizerís first clinical cancer vaccine program deploying a variety of vaccine platforms and immune modulators to build a multi-component vaccine-based immunotherapy regimen. Prior to joining Pfizer, Jooss served as vice president of Research at Cell Genesys, Inc. where she oversaw all research activities related to the company's cancer vaccine and oncolytic virotherapy programs.
Jooss received her Ph.D. in Molecular Biology from the University of Marburg in Germany and performed postgraduate work in gene therapy and immunology at the University of Pennsylvania. She is on the editorial board of Molecular Therapy and Journal of Gene Medicine and is a member of the immunology and educational committee for the American Society of Gene Therapy as well as the Industry Task Force of the Society for Immunotherapy of Cancer (SITC).