8:00 am Virtual Coffee & Online Registration
8:45 am Chair’s Opening Remarks
OPTIMIZING ANTIGEN SELECTION, PRODUCTION, & PRESENTATION
9:00 am Antigen Identification For Cancer Immunotherapy By Deep Learning On Tumor Hla Peptides
Synopsis
• Neoantigens are key tumor specific targets that may be targeted therapeutically
• Neoantigens can be identified for each patient using NGS and machine learning
• ctDNA can be used to evaluate neoantigen immunotherapies in the clinic
9:30 am Identification of Novel pHLA Targets for Solid Tumor Targeting with Cancer Vaccines
Synopsis
• Advantages of intracellular targets (pHLAs) versus viral, neoantigens or conventional cell surface antigens
• Strategies to find the most prevalent and immunogenic pHLA targets in tumors from CPI responders
• Selection of self-antigen targets with highest tumor vs normal ratios to avoid off-tumor, on-target toxicities
10:00 am Personalized Cancer Vaccines: Technologies to Screen Neoepitope Presentation
Synopsis
• Approaches to enhance presentation of epitopes from candidate neoantigens
• A high throughput targeted mass spectrometry approach for sensitive detection neo-epitope presentation
• Looking toward next generation protein sequencing technologies for neo-epitope discovery
10:30 am Morning Break & Speed Networking
11:15 am ERAP1 Inhibition To Alter Tumor Visibility And Trigger Differentiated T Cell Responses
Synopsis
• Tumor visibility, defined as the level of tumor-specific antigen expression, is shown to strongly correlate with response to checkpoint inhibition and is a vital aspect determining the immunogenicity within the tumor microenvironment
• Grey Wolf have developed inhibitors of ERAP1, an aminopeptidase in the antigen presentation pathway that determines which antigens are presented on the surface of a cell or tumor
• Grey Wolf ERAP1 inhibitors alter the immunopeptidome and thus visibility of the tumor, triggering a differentiated T cell response and causing tumor growth inhibition
11:45 am Identification Of Patient-Specific T Cell Neoantigens Through Hla-Agnostic Genetic Screens
Synopsis
• Identification of the T cell-recognized neoantigens in individual cancer patients is complicated by their patient-specific nature.
• We have developed the first genetic neoantigen discovery platform that allows identification of both CD4+ and CD8+ T cell-recognized neoantigens with high sensitivity and across complete HLA genotypes.
• This technology should facilitate the development of personalized neoantigen-based cancer
12:15 pm Whole Framome Cancer Vaccination Through Revolutionizing Neoantigen Detection
Synopsis
• Frame Therapeutics focuses on a class of neoantigens, termed Frames, which represent long and completely foreign stretches of amino acids resulting from frame-shift mutations and genomic rearrangements in the tumor genome.
• We show that our FramePro pipeline, combining a variety of sequencing technologies and bioinformatics analysis, can effectively identify all Frames expressed in cancer cells.
12:45 pm Lunch Break & Virtual Networking
CANCER VACCINE CASE STUDIES: mRNA, DNA, VIRAL VECTOR, & PEPTIDE CONTINUED
1:45 pm Rna-Encoded, Extended Half-Life Cytokines In Combination With Rna Vaccination For Synergistic Anti-Tumor Activity
Synopsis
• Optimized mRNA platform using lipid nanoparticle technology providing superior immunogenicity
• Proof of concept in an ongoing, first-in-human, dose-escalation phase I trial in patients with advanced melanoma (Lipo-MERIT) targeting nonmutated, shared tumor-associated antigens
• Combination with RNA-encoded, extended half-life cytokines for T cell modulation and enhanced anti-tumor activity
2:15 pm Leveraging Optimized DNA Plasmid Design and Delivery to Treat Glioblastoma Multiforme and Prostate Cancer
Synopsis
• Presentation of clinical trial data to show a DNA based cancer vaccine in combination with FLT3 ligand and PD-1 targeting metastatic castration resistant prostate cancer
• Updates on clinical status of a GBM vaccine in combination with cemiplimab (PD-1 inhibitor)
2:45 pm Identification of shared Neoantigens in Prostate Cancer
3:15 pm Afternoon Break & Speed Networking
3:45 pm Disrupting Glioblastoma: Survaxm Immunotherapy And Surviving Targeting Platforms
Synopsis
• SurVaxM is a novel cancer vaccine designed to stimulate an immune response targeting the tumor-specific antigen surviving
• A multi-center, single-arm phase 2a clinical trial of SurVaxM in survivinpositive newly diagnosed glioblastoma (nGBM, NCT02455557) is now complete
• Newly diagnosed glioblastoma patients were followed for safety, 6-month progression-free survival (PFS6), 12-month overall survival (OS12) and immunologic response
• SurVaxM immunotherapy generated encouraging efficacy and immunogenicity in nGBMand has minimal toxicity
• Trial design will be presented. Ongoing work with survivin and its tumor specific biology will be highlighted
4:15 pm Vaccination Against Shared Neoantigens Induced in Recurrent and Future Tumors
Synopsis
• A common set of neoantigens are induced in disseminated tumor lesions by tumor targeted siRNA mediated inhibition of the peptide transporter TAP.
• Vaccination against TAP downregulation induced neoantigens by targeted inhibition of TAP in resident dendritic cells Inhibited tumor growth in transplantable and autochthonous murine tumor models that was superior to vaccination against mutation-derived neoantigens, and was devoid of measurable toxicity.
• Vaccination against induced antigens using one or two broadly applicable chemically synthesized oligonucleotides will also benefit the majority of patients that do not express or express too few mutation derived neoantigens.
4:45 pm Development of a First-in-class Shared Neo-Antigen Vaccine for the Treatment of Prostate Cancer
Synopsis
• Data to show critical understanding of the tumor microenvironment to determine response to immune checkpoint therapy in combination with cancer vaccines
• Identification of VISTA as a potent inhibitory checkpoint that is predominantly expressed on CD68+ macrophages on PDACs, suggesting that VISTA may be a relevant immunotherapy target for effective treatment of patients with pancreatic cancer
5:15 pm Chair’s Closing Remarks
5:30 pm End of Day Two
