Cambridge Healthtech Institute’s 3rd Annual
Personalized Cancer Vaccines
August 30-31, 2018
Recent developments in personalized cancer vaccines are enabling the next generation of rational cancer immunotherapy. Cancer vaccines now may be combined with other immunotherapies, dendritic cells used for personalized immunotherapy, and neoantigens on the surface of cancer cells targeted, matching vaccine components to each patient. mRNA- and DNA-based vaccines present an additional opportunity for cancer therapeutics. Cambridge Healthtech Institute’s Third Annual Personalized Cancer Vaccines meeting will cover applications in several types of cancer and the progress in the understanding of the immune system that has significantly advanced the potential of cancer vaccines.
Final Agenda
THURSDAY, August 30
7:45 am Registration & Morning Coffee (Harbor Level)
8:25 Chairperson’s Opening Remarks
Nathaniel Wang, PhD, Head, Vaccines and Therapeutics, Viral Systems, Synthetic Genomics, Inc.
8:30 NEW: FEATURED PRESENTATION: Neoantigen-Based Vaccines for Breast Cancer
Glynn Wilson, PhD, Chairman and Strategic Advisor, TapImmune
Breast cancer causes 500,000 deaths each year. Rather than continue to add to the costs of treatment, we should advance promising approaches for prevention such as vaccination. One approach for a breast cancer vaccine is to target aberrantly expressed ‘self’ antigens. To produce such a vaccine, we’re aiming to achieve key milestones, namely identifying peptide epitopes from cancer antigens and identifying systems that induce durable T cell responses.
9:00 In situ Vaccination and the Power of Ignorance
Robert Pierce, MD, Scientific Director, Immunopathology Core, Fred Hutchinson Cancer Research Center
The presence of adaptive immune responses directed against tumor-associated antigens (TAAs) is critical for effective therapy with T cell checkpoint therapies, such as anti-PD-1. Many tumors are characterized by a lack of TILs (tumor infiltrating lymphocytes) even though they express potentially immunogenic antigens. We will discuss potential mechanisms of this “immunologic ignorance” phenotype, focusing on dysregulation of antigen presentation and processing machinery. The potential role for intratumoral IL-12 and other in-situ vaccination therapies to reverse this PD-1 non-responder phenotype will be discussed.
9:30 Development of a Rapid Personalized Self-Assembling Vaccine for Cancer
Mark C. Poznansky, MD, PhD, Director, Vaccine & Immunotherapy Center, Massachusetts General Hospital; Associate Professor, Harvard Medical School
We have developed a novel personalized self-assembling vaccine (SAV) for cancer that has the potential to be synthesized and delivered to the patient in 20 days. The vaccine consists of a fusion protein containing the broadly immune activating Mycobacterium tuberculosis derived heat shock protein 70 and avidin which self assembles with selected biotinylated immunogenic peptides derived from identified neoantigens. We have demonstrated proof-of-concept that SAV works in the context of generating T cell specific responses to infectious agents and we have begun work to show that this same function can be applied to generate effective T cell antigen specific responses in the context of preclinical murine models of ovarian cancer.
10:00 Coffee Break in the Exhibit Hall (Last Chance for Poster Viewing) (Commonwealth Hall)
10:45 Vaccibody’s Approach to Cost-Effective Personalized Cancer Neoantigen Vaccines Inducing a Unique CD8-Dominated T Cell Response
Agnete Fredriksen, PhD, President and CSO, Vaccibody AS
Vaccibody’s technology potentiates vaccines by attracting, activating and delivering antigens to antigen presenting cells which generates a unique CD8-dominated T cell response. By administering the DNA vaccine format of the Vaccibody vaccine, a rapid, cost-effective and robust manufacturing process can be applied which lends itself perfectly to develop commercially viable patient-specific vaccines on demand. A clinical study using targeted Vaccibody neoepitope DNA vaccines in multiple advanced cancer indications is ongoing.
11:15 Agenus’ Synthetic Neoantigen Vaccine Platforms, Including Novel Phosphopeptide Tumor Targets
Daniel Levey, PhD, Senior Director Vaccine Research, R&D, Agenus, Inc.
Agenus’ vaccine platform of synthetic neoantigens complexed to recombinant heat shock protein 70 (HSC70) and administered along with QS-21 Stimulon® adjuvant elicits an antigen-specific immune response in both mice and humans. Leveraging our in silico Agenus Immunogenic Mutation (AIM™) workflow, we are able to generate an optimal immunogenic vaccine blueprint for our AutoSynVax™ vaccines, which are uniquely designed and manufactured for each patient based on NGS profiling of their tumor. Our PhosphoSynVax™ vaccine is an off-the-shelf vaccine targeting a novel class of tumor neoantigens.
11:45 Development of Synthetic Self-Replicating RNA Platforms for Oncology Vaccines and Therapeutics
Nathaniel Wang, PhD, Head, Vaccines and Therapeutics, Viral Systems, Synthetic Genomics, Inc.
RNA as a vaccine and therapeutic modality has become a focus of significant interest. SGI has developed a self-amplifying RNA replicon that overcomes existing limitations and has shown improved protein expression, immunogenicity, and resistance to immune shutdown. This improved RNA replicon is also compatible with formulation technologies, which lower the effective dose required for immunization and improve cellular immunological memory. These engineered advantages enable novel applications of this platform for oncology vaccines and therapeutics.
12:15 pm Luncheon Presentation: Overcoming the Obstacles of Neoantigen Detection for Cancer Vaccine Development
Kedar Hastak, PhD, Field Applications Scientist, Personalis, Inc.
Conventional exome assays often have gaps in sequencing coverage, leading to missed neoantigens. Personalis developed the ACE ImmunoID platform to overcome this and other challenges for more comprehensive neoantigen identification. ACE ImmunoID combines augmented exome/transcriptome assays with state-of-the-art bioinformatics, optimized sample preparation, and automated processes to accelerate personalized cancer vaccine development.
12:45 Session Break
1:40 Chairperson’s Remarks
Nathaniel Wang, PhD, Head, Vaccines and Therapeutics, Viral Systems, Synthetic Genomics, Inc.
1:45 FEATURED PRESENTATION: Neoantigen Approaches as Personal and Precision Cancer Therapeutics
Richard Gaynor, MD, President, R&D, Neon Therapeutics
Neoantigens are important targets in directing the anti-tumor immune response and for the mechanism of action of checkpoint inhibitors. Our goal is to utilize multiple therapeutic options to target neoantigens in a variety of human tumors. One program, currently in the clinic, is utilizing a personal neoantigen vaccine in combination with a checkpoint inhibitor to treat patients with high mutation burden tumors in the metastatic setting. A second program is investigating ex vivo immunization of autologous T cells with neoantigens to generate both memory and naïve T cell responses that can be used for adoptive T cell therapy. The third program utilizes a precision medicine approach to identify neoantigens that are conserved in specific tumors for either vaccine or T cell based therapeutics. Together these three approaches will address the potential for personal and precision neoantigen-based cancer therapeutics.
2:15 Personalizing Cancer Vaccines Is More Than Just Whole Exome Sequencing
Bernard A. Fox, PhD, Chief, Laboratory of Molecular and Tumor Immunology, Providence Health & Services; CEO, UbiVac
The discovery of neoantigens, as one class of targets which the immune system uses to recognize cancer cells, has led to a flurry of activity around the development of vaccines containing the mutant peptide epitopes unique to a patient’s cancer. Some have described the application of this approach as personalized cancer vaccines. It is also well established that overexpressed and abnormally expressed proteins can serve as cancer antigens and these two classes of proteins dominate the National Cancer Institute’s list of 75 cancer antigens prioritized for translation. Developing a vaccine that targets all three classes of antigens: neoantigens, overexpressed and abnormally expressed proteins, potentially provides the immune system with greater breadth of immunity. Further, developing a vaccine that activates both T and B cell immunity, provides additional effector mechanisms that may defend against cancers that lose expression of MHC/HLA and escape T cell mediated destruction. However, the generation of a vaccine containing antigens unique to a patient’s cancer as well as those abnormally or overexpressed by that cancer, is only the first phase of personalizing a vaccine-based immunotherapy. A truly personalized approach needs to consider the immune “status” of the patient and tailor therapy to addresses defects in that immune status. Our group, in collaboration with partners, are developing a strategy that incorporates these components to develop a personalized cancer vaccine-based immunotherapy. A phase II trial of components of this strategy will be presented and prospects for future trials discussed.
2:45 Overcoming Challenges in Therapeutic Vaccine Design to Treat Cancer
Amitabha Chaudhuri, PhD, Vice President, Research & Development, MedGenome, Inc.
Prediction of cancer vaccines from somatic mutations is challenging. We present a machine learning-based approach to accurately identify cancer vaccines from tumor exome and RNA-seq data. The accuracy of prediction is demonstrated to be ~80% in an ex vivo T cell activation assay. MedGenome’s in-silico cancer vaccine prediction pipeline OncoPeptVAC enables efficient selection of optimum cancer vaccines for therapeutic use.
3:00 Immunomic is Addressing the Challenges of Viral Targets in Cancer
Bill Hearl, PhD, CEO, Immunomic Therapeutics, Inc.
The investigational UNITE platform was founded on a combination of complementary technologies and capabilities: ITI’s proprietary lysosomal targeting technology, optimal use of adjuvants, antigen selection and optimization, a breadth of delivery methods, and the ability to manufacture material at a large scale.
3:15 Refreshment Break (Commonwealth Hall)
3:45 Improving Checkpoint Blockade by Improving Tumor Antigen Cross-Presentation
Joshua Brody, MD, Assistant Professor, Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai; Director, Lymphoma Immunotherapy Program
Checkpoint blockade therapy of cancer has had tremendous impact, yet only a subset of patients responds. Although increased tumor mutational burden and tumor-associated antigen (TAA) load correlate somewhat with response to checkpoint blockade, we have shown that Hodgkin’s lymphoma, despite a high anti-PD1 response rate, has significantly fewer mutations than highly mutated tumors such as lung cancer. This demonstrates that response to checkpoint blockade is determined by factors beyond mutation burden. Our hypothesis is that checkpoint blockade is limited by suboptimal cross-presentation of TAA by suitably activated dendritic cells.
4:15 Th1 Epitopes for Versatile Tumor- and Patient-Tailored Vaccine Combination Therapies (VCT)
William C. Watt, PhD, President & CEO, EpiThany
Th1 epitopes from overexpressed tumor antigens constitute a rich source of active ingredients for cancer vaccine combination therapies (VCTs). Mining the “Th1 epitoire” for flexibility in vaccine antigen selection enables targeting of diverse tumors, patients and settings. EpiThany is incorporating its a priori validated tumor-specific Th1 epitopes into VCTs using multiple delivery platforms and combination agents to treat breast and ovarian cancers at multiple stages of disease.
4:45 Induction of Potent Neoantigen Targeted CD8+ T Cell Responses via Optimized DNA-Based Immunotherapy
Niranjan Y. Sardesai, PhD, CEO & President, Geneos Therapeutics
Tumor neoantigen targeting for the development of patient specific immunotherapies has emerged as a viable approach for cancer immunotherapy. Considerable efforts are being directed towards the accurate identification and prediction of targetable neoantigens for each patient. However equally critical is the platform deployed for the administration of the selected neoantigens to generate patient T cell responses in vivo. We will discuss the use of optimized plasmid DNA based approach.
5:15 End of Day
FRIDAY, August 31
7:45 am Registration (Plaza Level)
8:00 Breakout Discussion Groups with Continental Breakfast (Beacon Hill)
This session features discussion groups that are led by a moderator who ensures focused conversations around the key issues listed. Attendees choose to join a specific group, and the small, informal setting facilitates sharing of ideas and active networking. Details on the topics and moderators are available on the conference website.
9:00 Chairperson’s Remarks
Nathaniel Wang, PhD, Head, Vaccines and Therapeutics, Viral Systems, Synthetic Genomics, Inc.
9:05 An HLA-Agnostic Functional Neoantigen Discovery Platform for Personalized Cancer Vaccines
Stephen Schoenberger, PhD, Co-Director, San Diego Center for Precision Immunotherapy; Professor, La Jolla Institute for Allergy and Immunology
Accurate identification of patient-specific neoantigens (NeoAg) is essential to develop effective personalized cancer vaccines. We have developed WES/RNAseq-guided platform which combines a filtering algorithm based on sequencing metadata, rather than predicted HLA-binding, with in vitro functional T cell analysis. We report that >35% of selected expressed mutations can be verified as neoantigens in low mutational burden tumors by CD4+ and CD8+ T cells recognizing common activating mutations in driver oncogenes and numerous patient-specific “passenger” mutations.
9:35 Functional and Unbiased Neoantigen Calling as a Basis for Personalized Vaccines
Ezra Cohen, MD, Professor, Medicine, University of California, San Diego
Cancer presents a unique opportunity for the clinical application of precision immunotherapy due to the frequent expression of somatic mutations that can be recognized as tumor-specific neoantigens (NeoAgs) by a patient’s T cells. Meaningful translation of this concept, however, has been hampered by the lack of reliable methods for identifying NeoAgs in cancers of low mutational burden and by the absence of suitable preclinical animal models for evaluating and optimizing the ability of NeoAg-specific T cells to recognize and eradicate autologous tumors. Through a collaborative effort within the San Diego Center for Precision Immunotherapy 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. This platform has allowed effective identification of NeoAg in solid tumors with low-to-moderate mutational burden through precision immunotherapy which is now being applied as a vaccine using synthetic long peptides.
10:05 Rapid High-Throughput Functional Selection of Neoantigens and Assessment of Their Safety
Slavoljub Milosevic, PhD, Director, Technology Innovation, Medigene AG
Neoantigens are an important class of highly specific target molecules for specific vaccine and TCR-based immunotherapies. Identification of neoantigens by next-generation sequencing and prediction of binding to the HLA allotypes of a patient, still leaves open the issue of actual immunogenicity and safety of neoantigen targets for therapeutic use. Medigene combines high throughput functional screening with sophisticated in silico tools to overcome several current limitations in selecting relevant neoantigens.
10:35 Coffee Break (Plaza Level)
11:00 Harnessing the Innate Immunogenicity of Foreign Viral Antigens to Fight Solid Tumors
David Anderson, PhD, CSO, Research & Development, VBI Vaccines, Inc.
CMV is expressed on over 95% of glioblastoma, medulloblastoma and breast cancers. Like neoantigens, it provides an opportunity to target a non-self antigen that has inherently higher immunogenicity than traditional tumor associated antigens. Recently CMV-specific autologous approaches have demonstrated over a 2X increase in overall survival in glioblastoma. VBI’s approach utilizes its eVLP platform to restimulate CMV immunity by preferential uptake and presentation to dendritic cells. It offers an off-the-shelf approach to target CMV+ tumors.
11:30 Validation of Real Neoantigens with Mass Spectrometry
Harpreet Singh, PhD, President & CEO, Immatics US, Inc.
While neoantigens are a promising target class for immunotherapies in some patient populations, many researchers overlook that only a small fraction (presumably less than 1%) of all non-synonymous mutations are actually presented as pMHC targets and can thus act as neoantigens. Most strategies utilizing in silico prediction deliver more than 90% false-positive results. Such irrelevant antigens are currently often used in clinical trials and likely will not result in clinical benefit. Here, we show how Immatics’ proprietary XPRESIDENT platform, an ultrahigh-sensitivity, high-throughput, high-fidelity mass spectrometry setup allows to validate real neoantigens. Furthermore, data from clinical applications of highly personalized applications is shown underlining the promise of tailored immunotherapies using both neoantigens and shared antigens.
12:00 pm Close of Personalized Cancer Vaccines