Cambridge Healthtech Institute’s Inaugural

Neoantigen-Based Personalized Immunotherapies

Biomarkers, Cancer Vaccines and Translational Strategies

December 6-7, 2017 | Hilton San Diego Resort | San Diego, CA


Increasing the number of patients that respond successfully to cancer immunotherapies is the next big step in the fight against cancer. Recent studies have shown that the more tumor-specific mutations, or neoantigens, the cancer cells have, the greater the chance that the tumor will not be tolerated by the immune system. With increasing access to next generation sequencing (NGS) technologies, cancer researchers are scouring the tumor genome, including the mutanome, to find new therapies. Cambridge Healthtech’s Inaugural Neoantigen-Based Personalized Immunotherapies is proud to discuss the cutting-edge research that combines cancer, immunology and NGS to design the next generation of personalized cancer immunotherapies.

Final Agenda

WEDNESDAY, December 6

12:00 pm Conference Registration

12:15 Enjoy Lunch on Your Own

12:45 Dessert Break in the Exhibit Hall with Poster Viewing


1:15 PLENARY KEYNOTE SESSION click here for more information
Manufacturing Chimeric Antigen Receptor T Cells for Early Phase Clinical Trials
David F. Stroncek, M.D., Chief, Cell Therapy Section, Transfusion Medicine, NIH Clinical Center
Evolution of Cancer Immunotherapy
Ramy Ibrahim, M.D., VP, Clinical Development, Parker Institute for Cancer Immunotherapy

2:50 Refreshment Break in the Exhibit Hall with Poster Viewing

IDENTIFYING IMMUNOGENIC NEOANTIGENS – BIOINFORMATIC APPROACHES

3:30 Chairperson's Opening Remarks

Pamela Carroll, Ph.D., Senior Vice President, Immuno-oncology, Genocea Biosciences

3:35 KEYNOTE PRESENTATION: Neo-Antigens in Cancer Immunotherapy: Where Are We and Where Are We Going?

Radvanyi LaszloLaszlo Radvanyi, Ph.D., Senior Vice President, Senior Scientific Advisor, Immunology, Immuno-Oncology, EMD Serono

This talk will present the history and status of the emerging field of neo-antigen (mutanome) targeting in cancer immunotherapy. Current approaches used to identify cancer neo-antigen epitopes along with examples of how neo-antigens are being targeted in cancer immunotherapy clinical trials will be presented. How the mutanome is being used as a biomarker in immunotherapy will also be described. Finally, some of the current obstacles being faced in the field will be discussed along with a summary of the strategic position and future impact of neo-antigen targeting in the overall cancer immunotherapy landscape.

4:05 How to Find a Neoantigen in silico: Insights from the Tumor Neoantigen Selection Alliance

Danny_WellsDanny Wells, Ph.D., Scientist, Informatics, Parker Institute for Cancer Immunotherapy

It is now accepted the mutation-derived neoantigens can elicit an anti-tumor immune response and may potentially drive a substantial part of it. Identifying neoantigens accurately from the exome sequence of a tumor could have immense therapeutic benefit but remains a steep challenge. Here I will discuss our efforts at the Parker Institute to understand i) what makes a neoantigen immunogenic and ii) what algorithmic approaches are best at identifying immunogenic neoantigens. In particular, I will describe new results from our consortium effort in this area, the Tumor Neoantigen Selection Alliance.

4:35 Immunogenic Determinants of Tumor Neoantigens

Suchit Jhunjhunwala, Ph.D., Scientist, Bioinformatics & Computational Biology, Genentech

Neoantigens can drive anti-cancer immunity. This has generated high interest in using neoantigens for personalized cancer vaccination. Computational predictions can prioritize neoantigens that may be presented by MHC molecules. However, false positives remain, and understanding properties of immunogenic neoantigens may help further enrich for them. We vaccinated naive mice with mutated long peptides to identify immunogenic neoantigens, and investigated their properties that may help further prioritize immunogenic neoantigens.

5:05 Close of Day

THURSDAY, December 7

8:00 am Breakfast Breakout Roundtable Discussions

 Cancer Vaccines
Moderators: Karin Joos, Ph.D., CSO, Gritstone Oncology
Aaron M. Miller, M.D., Ph.D., Assistant Clinical Professor of Medicine, UC San Diego Health, Moores Cancer Center

  • Strategies for combination therapies
  • The challenges in cancer vaccine standardization 
  • Regulatory concerns for the future

 Neoantigens as Biomarkers for Cancer Immunotherapy

Moderators: Matthew M. Gubin, Ph.D., Instructor, Schreiber Lab, Pathology and Immunology, Washington University School of Medicine 

Pamela Carroll, Ph.D., Senior Vice President, Immuno-oncology, Genocea Biosciences  

  • Advances to improve monitoring of neoantigen responses
  • Implementation of immunomonitoring platforms into clinical trials
  • Monitoring neoantigen responses in tumor versus peripheral tissue
  • WORKING WITH MHC CLASS 1

    8:55 Chairperson's Opening Remarks

    Matthew M. Gubin, Ph.D., Instructor, Schreiber Lab, Pathology and Immunology, Washington University School of Medicine

    9:00 Technologies for Personalized T Cell Receptor Engineered Cancer Immunotherapies

    James HeathJames R. Heath, Professor of Physics, Chemistry, California Institute of Technology

    We are particularly concerned with Class I MHC (mutated) neoantigen-CD8+ T cell recognition. In principle, neoantigens that draw T cells into a tumor can comprise personalized vaccines, and the T cell receptors (TCRs) that recognize those neoantigens can be engineered as personalized cellular therapies. I will discuss our approach, called nanoparticle-barcoded nucleic acid cell sorting (NP-barcoded NACS), designed for enumerating neoantigen-specific T cell populations from non-expanded tumor infiltrates or peripheral blood, and for pairing those neoantigen-specific CD8+ T cell populations with the cognate TCRa/b gene, using single cell sequencing methods.

    9:30 Immunotherapeutic Responses to Cancer Neoantigens

    Matthew GubinMatthew M. Gubin, Ph.D., Instructor, Schreiber Lab, Pathology and Immunology, Washington University School of Medicine

    Recognition of tumor-specific mutant neoantigens can drive the anti-tumor effects of immunotherapy. We previously developed a method to reliably predict MHC class I cancer neoantigens. This has allowed us to delineate mechanisms of effective checkpoint blockade therapy and develop personalized immunotherapies targeting neoantigens in preclinical models of which are now being tested in patients. The goal of our work is to better understand anti-tumor T cell responses and to develop safer, more specific and more effective immunotherapy as well as improved patient immunomonitoring.

    OncoImmunity10:00 An Integrated Machine-Learning Approach to Improve the Prediction of Clinically Relevant Neoantigens

    Trevor Clancy, Ph.D., CSO, OncoImmunity

    Current neoantigen discovery algorithms may not be optimal to predict presentation to the cell surface. Here, we outline a high-performing machine learning approach, trained on mass-spectrometry data, that predicts naturally processed and presented antigens. The predictor is integrated with several immune parameters, such as HLA binding, in a deep learning layer to predict bone fide neoantigens. We illustrate its application to significantly improve the identification of neoantigen targets for personalized cancer immunotherapy.

    10:30 Networking Coffee Break

    IDENTIFYING IMMUNOGENIC NEOANTIGENS- CONT

    10:55 Identifying Immunogenic Neoantigens: Turning Tumor Mutations into Personalized Cancer Therapies

    Karin JoosKarin Joos, Ph.D., CSO, Gritstone Oncology

    DNA damage may cause mutations in tumors that can generate new antigens, known as tumor-specific neo-antigens (TSNAs), which were identified to be T-cell targets in clinical responders on immune checkpoint therapy. To increase responder frequency in clinic, Gritstone Oncology is applying a proprietary model that accurately identifies TSNAs and seeks to deliver them in the context of potent viral vector based vaccine platforms which have shown to induce hi-titer, polyfunctional and durable CD4+ and CD8+ T-cell responses in humans. The personalized vaccine is delivered in combination with immune checkpoint blockade, to keep TSNA-induced T-cells active in the immunosuppressive tumor microenvironment.

    11:25 Comprehensive Discovery of Tumor Antigens for Better Personalized Vaccines

    Pamela Carroll, Ph.D., Senior Vice President, Immuno-oncology, Genocea Biosciences

    By screening T cells in the natural context of patient disease with antigens presented by autologous dendritic cells, ATLAS detects bona fide antigens. ATLAS-discovered antigens have limited overlap with those identified by in silico methods and are classified as stimulatory or inhibitory modulators of T cell activity. ATLAS powered personalized neoantigen vaccines are planned to start in 2018.

    11:55 Letting Biology Drive Neoantigen Discovery

    Aaron M. Miller, M.D., Ph.D., Assistant Clinical Professor of Medicine, UC San Diego Health, Moores Cancer Center

    Through a collaborative effort between UCSD and LJI we have developed a set of novel bioinformatic and cellular tools which allows for the functional validation of NeoAg recognized by both CD4+ and CD8+ T cells at a higher rate than previously reported. We have also applied a novel cellular reprogramming technology which allows for the routine generation of patient-specific xenograft cell lines that preserve expression of identified neoantigens and are recognized by a patient’s autologous T cells in vitro and in vivo as tumors growing in immunodeficient NSG mice. This has allowed effective identification and targeting NeoAg in solid tumors with low to moderate mutational burden through precision immunotherapy.

    12:25 pm Enjoy Lunch on Your Own

    12:55 Session Break


    Clinical Applications - Antibodies and Cancer Vaccines

    1:55 Chairperson's Opening Remarks

    Philip M. Arlen, M.D., President & CEO, Precision Biologics, Inc.

    2:00 The Discovery and Development of Novel Monoclonal Antibody, NEO-201 Targeting a Novel Neoantigen

    Philip ArlenPhilip M. Arlen, M.D., President & CEO, Precision Biologics, Inc.

    Immunogenic neoantigens were derived from a membrane preparation of pooled allogeneic colorectal cancer from patients undergoing surgery. Membrane fractions were isolated and tested for immunogenicity and utilized in a clinical trial in patients with chemotherapy refractory metastatic colorectal cancer. A positive correlation was observed in patients who were able to mount and sustain IgG responses to vaccine. Antibodies were screened using this vaccine and tested for sensitivity, specificity, and anti-tumor function. A novel monoclonal antibody, NEO-201, has demonstrated preclinical antitumor activity with sensitivity and specificity to several tumor types. First in man clinical studies are planned for 2017.

    2:30 Combining a Potent Vaccine Technology with Patient-Specific Neoepitopes to Generate Commercially Viable Individualized Cancer Vaccines

    Agnete Fredriksen, Ph.D., CSO, Vaccibody

    Vaccibody has developed a unique platform technology able to substantially potentiate vaccines, able to attract, activate and deliver antigens to antigen presenting cells. By using the DNA vaccine format encoding for the Vaccibody protein, a rapid, cost-effective and robust manufacturing process has been generated which lends itself perfectly to develop commercially viable patient-specific vaccines on demand. Supportive preclinical data with neoantigen based DNA vaccines as well as clinical data with a similar Vaccibody DNA vaccine using viral antigens support a favourable safety, tolerability and efficacy profile. A clinical study using targeted Vaccibody neoepitope DNA vaccines in multiple advanced cancer indications is under preparation.

    3:00 Networking Refreshment Break

    3:15 An Immunogenic Personal Neoantigen Vaccine for Patients with Melanoma

    Patrick OttPatrick Ott, M.D., Dana-Farber Cancer Institute

    We designed a multi-epitope personalized neoantigen vaccine targeting tumor neoantigens consisting of up to 20 synthetic long peptides containing tumor neoepitopes together with the Toll Like Receptor 3 agonist poly-ICLC. We tested this vaccine approach in a Phase I study in patients with previously untreated high-risk melanoma and find that this approach is feasible, safe, and immunogenic, providing a strong rationale for further development of this personalized vaccine approach.

    3:45 Stability Matters: Neoscreen

    Sune JustesenSune Justesen, CSO, Immunitrack

    Many different approaches are taken to identify good neo-antigens. Immunitrack is a spin-out from the academic group that developed netMHC and has an extensive recombinant MHC platform and accompanying affinity and stability assays as well as tetramers. We will try and give a view of how confirmed neo-epitopes look like from an in vitro assay point of view, and show how our platform can be used to identify them.

    4:15 CLOSING PANEL DISCUSSION: Future Directions for Neoantigen Based Therapies

    Moderator: Philip M. Arlen, M.D., President & CEO, Precision Biologics, Inc.

    • How can we deal with scaling personalized therapies?
    • How can we standardize neoantigen selection?
    • What lies in the future for personalized therapies?

    4:45 Close of Neoantigen-Based Personalized Immunotherapies