Gritstone presents advances in neoantigen vaccine programs, capabilities

Gritstone bio is delivering three presentations related to the company’s neoantigen vaccine programs and capabilities at the 2023 American Association for Cancer Research Annual Meeting in Orlando, Florida. GRANITE Phase 1/2 Presentation: Disease monitoring with comprehensive genomics provides evidence of mechanism of action and immune evasion in patients receiving an individualized neoantigen cancer vaccine. Key Highlights: Comprehensive ctDNA longitudinal monitoring enables real-time assessment of clinical response and acquired resistance; Paired pre- and post-vaccine biopsy analyses show upregulation of gene signatures associated with immune infiltration, supporting T cell expansion and induction of dynamic T cell receptor repertoire changes in the tumor and periphery; Majority of neoantigens are retained in tumor even after patient receives treatment prior to GRANITE administration. EDGE Presentation: Language modeling of peptide-HLA interactions achieves state-of-the-art performance on prediction of peptide presentation by HLA Class II. Key Highlights: While cytotoxic CD8+ T cells are critical to tumor control and clearance, CD4+ T cells can play a key role for the induction component of durable anti-tumor responses; Accurate prediction of immunogenic HLA Class II restricted neoantigens, which drive CD4+ T cell response, can further vaccine immunogenicity and durability; Gritstone’s EDGE platform capabilities have been enhanced to include state-of-the-art immunogenicity prediction of peptide presentation by HLA Class II with significant performance improvements over current approaches; Expanding the prediction capabilities of EDGE to include both HLA Class I and II neoantigens can help identify neoantigens with potential to mount broader and more robust overall immune responses. SLATE Phase 1/2 Presentation: HLA-DR-restricted CD4+ T cell responses to KRAS G12C in healthy donors linked to bacterial mimotope: lessons for KRAS neoantigen vaccines in cancer patients. Key Highlights: Vaccines targeting KRAS mutations may overcome the challenges of acquired resistance encountered with small molecule-based approaches targeting KRAS mutations; Study links CD4+ T cell responses to KRAS G12C in healthy donors to a bacterial mimotope; Data from healthy donors and from a SLATE patient show responses to KRAS G12C are driven by CD4+ T cells with cytotoxic capabilities likely driven by TCRs with cross-reactivity to a bacterial mimotope; SLATE induction of both CD8+ and CD4+ T cell responses may expand patient eligibility to potentially include subjects harboring a KRAS G12C mutation irrespective of HLA alleles.