Cambridge Healthtech Institute 제3회

Personalized Cancer Vaccines

(맞춤형 암백신)

2018년 8월 30일-31일


맞춤형 암백신을 테마로 한 이 컨퍼런스 프로그램에서는 각종 암에 대한 백신 사용 및 암백신의 가능성을 크게 확대한 면역계에 관한 연구 진전 등의 토픽이 다루어집니다.


Final Agenda

8월 30일(목)

7:45 am Registration & Morning Coffee

맞춤형 암백신

8:25 Chairperson's Opening Remarks

Nathaniel Wang, PhD, Head, Vaccines and Therapeutics, Viral Systems, Synthetic Genomics, Inc.


8:30 FEATURED PRESENTATION: Neoantigen-Based Vaccines for Breast Cancer

Keith Knutson, PhD, Director, Cancer Vaccine & Immune Therapies Program, Mayo Clinic

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)

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 (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:45 Session Break

병용요법을 위한 맞춤형 백신

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 naive 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 Sponsored Presentation (Opportunity Available)

3:15 Refreshment Break

3:45 Developing Cancer Vaccines in the Era of Checkpoint Blockade: Avoiding the T Cell Trap

Yared Hailemichael, PhD, Research Instructor, Melanoma Medical Oncology, The UT MD Anderson Cancer Center

One strategy being explored as an avenue to increase T cell immunity is vaccination. Here, we show that a commonly used experimental vaccine formulation causes local inflammation at the vaccination site becoming a trap for anti-CTLA-4 and anti-PD-(L)1 induced tumor-specific T cells. New findings point the way to rational design and selection of cancer vaccine formulations that synergize with checkpoint blockade therapy.

4:15 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.

4:45 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.

5:15 End of Day

8월 31일(금)

8:00 am Breakout Discussion Groups with Continental Breakfast

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.

맞춤형 면역치료를 위한 신항원의 식별과 선택

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

Dolores Schendel, CEO & CSO, Medigene

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

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 A New Source of Highly Immunogenic Neoepitopes for Cancer Vaccines

Stephen Albert Johnston, PhD, Director, Center for Innovations in Medicine; Professor, School of Life Sciences, Biodesign Institute, Arizona State University; CEO, Calviri, Inc.

Mistranslation through microsatellites and mis-splicing produce 100x more neoantigens than DNA mutations. Frameshifts (FS) produced by mis-translation and splicing are highly immunogenic. These FS are protective in mouse models; humans and dogs with cancer raise immune responses to these FS, which can be detected using a rapid peptide array. In a mouse model this array-based system can be used to rapidly create a personal vaccine that shows protection.

12:30 pm Close of Personalized Cancer Vaccines

* 주최측 사정에 따라 사전 예고없이 프로그램이 변경될 수 있습니다.

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