Friday November 16, 2018
08.45 Chair’s Opening Remarks
09.00 Neoantigen Approaches as Personal and Precision Cancer Therapeutics
- Richard Gaynor President of R&D, Neon Therapeutics
- Neon Therapeutics is a clinical-stage immuno-oncology company that utilizes multiple therapeutic modalities, and both personal and precision approaches, to target neoantigens in a variety of human tumors.
- Neon’s approach in the personalized vaccine setting currently includes utilizing a personal neoantigen vaccine in combination with a checkpoint inhibitor and, in certain cases, chemotherapy, to treat patients with high mutational burden tumors in the metastatic setting. As part of Neon’s personalized T cell approach, Neon is investigating ex vivo immunization of multiple T cell populations that are generated to target each individual patient’s unique set of neoantigens.
- Finally, as part of Neon’s precision approach, Neon is working to identify neoantigens that are conserved in specific tumors across a broader spectrum of patients and can be adapted for treatment through either vaccine or T cell based therapies.
09.30 Improved induction of neoantigen-specific T cells with self-assembling nanoparticles
- Geoffrey Lynn Chief Executive Officer, Avidea Technologies
- Properties of peptide-based vaccines that impact CD8 T cell induction
- Self-assembling nanoparticles allow rapid, reliable manufacturing and enhanced CD8 T cell induction
- Validation of epitope prediction algorithms in mice
- Primate models for translation
10.00 Optimization of cancer vaccine development by using Multiplexed Identification of T-cell Receptor Antigen Specificity (MIRA)
- Mark Klinger Head of TCR Discovery, Adaptive Biotechnologies
- Generating immunogenicity data to antigens of interest at scale informs antigen selection for improved vaccine design and development.
- Adaptive Biotechnologies has developed a novel, highly sensitive approach known as Multiplexed Identification of T cell Receptor Antigen specificity (MIRA).
- MIRA combines high-throughput T-cell receptor (TCR) repertoire sequencing with conventional immune techniques to assess T cell specificity to hundreds query antigens at a time with a sensitivity of one in 10 million naïve human T cells.
- To validate this approach, we assessed biologically relevant T-cell immune responses against more than 350 neoepitopes using T cells sourced from the naïve repertoire of 50 healthy donors to leverage the massive diversity of the naïve TCR repertoire and identify ultra-low frequency antigen-specific T cell responses.
10.30 Morning Refreshments & Networking
11.00 Identification and Characterization of Presented Tumour Neo- Epitopes from Metastatic Colon Cancer
- Primary cancer data
- Metastatic cancer
- Normal tissue expression
- Functional characterisation
Eustache Paramithiotis, Vice President, Discovery, Caprion Biosciences
11.30 Presentation of MHC Bound Phophopeptides from Primary Patient Tissue Enables the Identification of Prevalent Molecular Targets for Vaccines and Cell Therapy
- Post-translational modification is central to the control of cellular pathways and are critical to a transformed cancerous state.
- The presentation of phosphopeptides on MHCs follows distinct allele preferences that reflect both the anchors required for strong MHC binding and motifs that mirror dysregulated kinases pathways. We will describe these.
- Identification of clear immune responses to phosphopeptides and not to unmodified peptides reflects the role of phosphorylation in breaking tolerance. Experiments showing immune responses in mouse experiments post vaccination will be described. In addition, highly specific TcRs to phosphopeptide
Dennis Underwood, Vice President of Molecular & Information Systems, Agenus
12.00 Identification of Tumor-resident and Circulating Neoantigen-specific Lymphoctyes
- OIdentification of neoantigen-specific lymphocytes from the tumor and peripheral blood
- Identification of neoantigens in patients with low mutation burden
- Comparison of techniques available for identification of personalized neoantigens
Alena Gros, Group Leader, Tumor Immunology & Immunotherapy
11.00 TG01 - A Neo-antigen Specific Peptide Vaccine Targeting RAS Mutations in Solid Tumors
- RAS mutations, a well characterised neo-antigen and therefore a most attractive target
- TG01, a 7 peptide vaccine able to cover 98% of RAS mutations in pancreas cancer
- Encouraging phase II clinical data using
- TG01 in combination with adjuvant chemotherapy in resected pancreas cancer
Magnus Jaderberg, Chief Medical Officer, Targovax
11.30 Heat Shock Protein Chaperoned Synthetic Peptide Cancer Vaccines
- Vaccine format: Heat shock protein noncovalently complexed peptides
- Use of the protein chaperone is dose sparing, reduces amount of antigenic peptide required
- Vaccine is adjuvanted with clinically validated QS-21
Mark Findeis, Senior Director Research Biochemistry, Agenus
12.00 Adjuvants for Peptide based Cancer Vaccines – are we there yet?
- What are vaccine adjuvants – a general overview
- Why are adjuvants crucial for Neoantigen-based Cancer Vaccines
- What adjuvants does the cancer vaccine field use and are they good enough?
Dennis Christensen, Head of Vaccine Adjuvant Research, Statens Serum Institute
12.30 Lunch & Networking
13.30 Development and Testing of Cancer-type Specific Vaccines based on Frameshift Neoantigens
- Recurrent frameshift neoantigens are produced in tumors in RNA processing
- Immune reactions to the FS neoantigens can be detected by a simple blood assay
- Vaccines focused on particular cancer types can be pre-made from common FS neoantigens
Stephen Johnston, Chief Executive Officer, Calviri
14.00 High Tumor Burden Mandates a Cancer Vaccine Targeting many Neoantigens
- Great Apes Ad (GAd) vaccination is highly effective as stand-alone treatment in an early therapeutic setting
- Large established tumors are resistant to cancer vaccination
- Resistance can be overcome by a vaccine targeting many neoantigens combined with immunomodulators
Elisa Scarselli, Chief Scientific Officer, Nouscom AG
14.30 Vaccinating Against Neoantigens Induced in Concurrent and Future Tumors
- Experiments in advanced murine tumor models have shown that the approach was devoid of measurable toxicity, and was superior to vaccinating against “personalized” neoantigens
- Vaccinating against induced neoantigens overcomes the main limitations of targeting endogenous tumor neoantigens, generating clonal neoantigens, preventing immune evasion, and applicable to all patients (including the majority of patients that do not expressing endogenous neoantigens)
Eli Gilboa, Professor & Director of Dodson Interdisciplinary
Immunotherapy Institute at Miller School of Medicine,
University of Miami
15.00 A Novel Small-molecule Approach to induce Denovo Neoantigen Creation
- NeoPhore is creating drug inhibitors of DNA mismatch repair for cancer immunotherapy
- Mismatch repair is a highly validated target: genetic MMR deficiency generates neoantigens and
- checkpoint blockade sensitivity in both lab and clinical settings
- Mismatch repair inhibitors should exhibit efficacy across many cancer types, in combination with both checkpoint blockade and other immunostimulatory strategies
Jeff Roix, Chief Executive Officer, NeoPhore
13.30 Interrogating the right signals to induce the right Immune Response
- ”Danger” signals, not ”stranger” signals, as the main promoters of DC-mediated cross-priming of MHC class I restricted CD8+ T cells
- Allogeneic, off-the-shelf, ”stranger”-stimulated DCs (alloDCs) promote efficient ”danger”-mediated crosspriming of CD8+ T cells by endogenous ”bystander” DCs
- The adenovector Ad5PTDf35 efficienty transduce alloDCs with with genes coding for tumor-specific antigens
Alex Karlsson-Parra, Co-Founder & Chief Scientific Officer, Immunicum AB
14.00 Meeting the Neoantigen Vaccine Challenge with Virotherapeutics
- The place of neoantigen vaccines in the immunotherapeutic landscape
- Engineering improvements of viral vaccines for enhanced immunogenicity and efficacy
- Rethinking manufacturing paradigms to reduce lead time, cost and environmental impact of bespoke vaccines.
Kaïdre Bendjama, Project Leader, Personalized Vaccines, Transgene SA
14.30 Manufacturing, Regulatory and Logistics Challenges in the Rapidly Evolving Area of Individualized Therapeutic Cancer Vaccines: The Road to FASTdna at a low cost One-Stop-Shop
- Plasmid DNA vaccine
- Game changing regulatory environment
Mette Husbyn, Chief Technical Officer, Vaccibody
15.00 Strategic Management of COGs and Manufacturing Turnaround for Personalized Cancer Vaccine Development
- Setting targets
- Identifying and assessing opportunities
- Prioritizing improvement projects
Marc Wolfgang, Vice President of Technical Operations, Neon Therapeutics
15.30 Mechanisms of Immune Suppression in the Tumor Microenvironment
- Keith Knutson Professor of Immunology, Mayo Clinic
- Understand the multiple mechanisms of immune suppression that are utilized by cancers to evade immune-mediate destruction
- Understand mechanisms underpinning the therapeutic efficacy of inhibitors of the PD-1/PD-L1 immune regulatory axis
- Understand emerging strategies to reverse local immune suppression in the tumor microenvironment