Cambridge Healthtech Institute’s Second Annual
Personalized Cancer Vaccines and Neoantigen Targeted Therapies
Personalized Cancer Immunotherapy in the Genomic Era
August 31-September 1, 2017 | Sheraton Boston | Boston, MA
Fueled with advances in genomic technologies, personalized oncology promises to innovate cancer therapy and target previously undruggable space. Developments in NGS technology enabled systematic analysis of patient-specific mutanome and open the door to developing personalized cancer vaccines targeting neoantigens. The personalized vaccines used alone or in combination with other immunotherapies are enabling the next generation of cancer therapy. Cambridge Healthtech Institute’s Second Annual Personalized Cancer Vaccines and Neoantigen Targeted Therapies meeting brings together thought leaders from pharmaceutical and biotech companies, leading academic teams and clinical immuno-oncologists to share research and case studies in implementing patient-centric approaches to using the immune system to beat cancer, including utilizing NGS to identify tumor-specific neoantigens, using in silico tools to predict immunogenic neoepitopes, and targeting them with personalized vaccines or vaccine combination therapies.
Final Agenda
THURSDAY, August 31
7:45 am Registration & Morning Coffee
8:25 Chairperson’s Opening Remarks
Joshua Brody, M.D., Director, Lymphoma Immunotherapy Program, Icahn School of Medicine at Mount Sinai
8:30 Discovery of the Best Checkpoint Blockade Partner for in situ Vaccination
Joshua Brody, M.D., Director, Lymphoma Immunotherapy Program, Icahn School of Medicine at Mount Sinai
Checkpoint blockade therapy has had tremendous impact, but for many tumors, despite sufficient tumor antigen load, suboptimal cross-presentation of these antigens precludes effective CD8 T cell activation. To address this problem, we developed a novel in situ vaccine combining intratumoral Flt3L to recruit DC, radiotherapy to load DC with TAA, and intratumoral TLR agonist to activate loaded DC. An early phase trial testing this approach has demonstrated partial and complete systemic tumor regressions at distant (untreated) tumors. Ongoing work is focused on discovery of the optimal checkpoint blockade to combine with this approach.
9:00 Cancer Vaccines in the Era of Checkpoint Blockade
Willem W. Overwijk, Ph.D., Professor, Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center
Recent developments in T cell checkpoint blockade therapy, next-generation sequencing and molecular immunobiology open new possibilities and new questions for cancer vaccines. Based on clinical data and animal models, we discuss where cancer vaccines fit in the current clinical landscape of immune-based therapies, which antigens should go into a personalized cancer vaccine, what makes a powerful cancer vaccine adjuvant, and what could move cancer vaccines from “promising” to “effective.”
9:30 Driving CD8+ T Cell Responses to Mutational Neoantigens in Tumors – Harnessing Immunogenic Viral Vectors
Karin Jooss, CSO, Gritstone Oncology
DNA damage may cause mutations in tumors that can generate new 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.
10:00 Coffee Break in the Exhibit Hall (Last Chance for Poster Viewing)
10:45 KEYNOTE PRESENTATION: Genetically Engineered DC Vaccines for Melanoma
Lisa H. Butterfield, Ph.D., Professor, Medicine, Surgery and Immunology, University of Pittsburgh
Cancer vaccines are designed to promote antitumor immunity. There are many approaches which have been tested clinically: different forms of antigens, different adjuvants, DNA and RNA, viral vectors and allogeneic or autologous cells. Dendritic cells (DC) have been tested in many forms, with strong evidence for immunogenicity and limited evidence for clinical activity. We recently completed a DC vaccine trial with antigen-engineered autologous DC for melanoma, and immune monitoring results will be presented.
11:15 Development of ICT-107, a Novel Dendritic Cell Immunotherapy against Glioblastoma
Steven J. Swanson, Ph.D., Senior Vice President, Research, ImmunoCellular Therapeutics, Ltd.
ICT-107 is a novel dendritic cell immunotherapy targeting cancer stem cells that is being evaluated in a Phase III trial in newly diagnosed glioblastoma. The results from the early clinical trials influenced the design of the multi-center international Phase III trial. The design, manufacturing challenges, survival data, and immune monitoring data for ICT-107 are described.
11:45 Dendritic Cell Immunotherapy for Solid Tumors
Marnix Bosch, Ph.D., CTO, Northwest Biotherapeutics
The capacity of dendritic cells (DCs) to initiate adaptive immune responses can be harnessed for cancer immunotherapy purposes. Northwest Biotherapeutics has developed two product lines in which autologous DCs are utilized to present tumor antigens to the immune system, with the goal to affect tumor growth and extend patients’ lives in the absence of significant toxicity. These products are being tested in both late stage and early stage clinical trials in which both the efficacy of the products as well as the scientific underpinnings of the technology are being further evaluated.
12:15 pm ctDNA Guided Drug Development
Kalidip Choudhury, Ph.D., Head, Search and Evaluation, Natera, Inc.
There is an urgent need to increase the efficacy of current oncology therapy and better target its use. An attractive feature of liquid biopsies is the potential to monitor tumor progression and response to therapy in a minimally invasive manner. We discuss our recent findings on the use of patient specific ctDNA profiling to characterize the subclonal dynamics of solid tumors and identify drug resistance. These studies indicate that drug development guided by ctDNA platforms to identify residual disease, define adjuvant treatment response and target emerging subclones are now feasible.
12:30 Sponsored Presentation (Opportunity Available)
12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:15 Session Break
2:25 Chairperson’s Remarks
Keith Knutson, Ph.D., Director, Cancer Vaccine & Immune Therapies Program, Mayo Clinic
2:30 Presentation to be Announced
3:00 Talk Title to be Announced
Lelia Delamarre, Ph.D., Group Leader, Cancer Immunotherapy Department, Genentech
3:30 Refreshment Break
4:00 In vivo Delivery of Multiple Conserved Tumor Antigens, Neoepitopes and Immune Response Enhancers with Dendritic Cell Targeting Lentiviral Vector Zvexmulti
Jan ter Meulen, M.D., CSO, Immune Design
Given the current limitations of accurately predicting immunogenic CD4 and CD8 T-cell tumor neoepitopes, we propose that a patient-specific combination of multiple neoepitopes and conserved tumor antigens may increase the efficacy of immunotherapy. To this end, we have modified our dendritic-cell targeting integration deficient lentiviral vector platform ZVex to express any combination of antigens and immune-enhancers concomitantly. ZVexMulti is a novel plug-and-play system for rapid generation of fully personalized cancer immunotherapies.
4:30 Generation of Cost-Effective and Immunogenic Private Neoantigen-Based DNA Vaccines
Agnete Fredriksen, Ph.D., CSO, Vaccibody
DNA vaccines represent an attractive vaccine format for manufacturing patient-specific neoantigen-based vaccines on demand due to its robust, cost-effective and rapid manufacturing method. Vaccibody has developed a unique platform technology able to substantially potentiate DNA vaccines by targeting neoantigens to antigen presenting cells, without increasing manufacturing complexity. Custom-made neoepitope prediction tools validated by in vivo studies are used to optimize chances of clinical efficacy in the upcoming clinical study.
5:00 Autosynvax™ (ASV™), a Personalized Second Generation Vaccine Platform
Jean-Marie Cuillerot, M.D., CMO, Agenus
AutoSynVax™ (ASV™) vaccines contain patient-specific peptides with defined immunogenic epitopes resulting from specific mutations within a patient’s tumor, deduced using a proprietary algorithm, complexed with a recombinant HSP molecule (HSC70) and delivered with a saponin-based adjuvant. Preclinical studies demonstrate that heat shock protein-driven presentation of synthetic tumor neo-peptides evokes an anti-tumor immune response as well as lasting immune memory in murine cancer models.
5:30 End of Day
6:00 Dinner Short Course Registration*
SC4: CRISPR/Cas9 Applications in Immunotherapy
*Separate registration required, please click here for more information.
FRIDAY, SEPTEMBER 1
8:00 am Registration and Morning Coffee
8:25 Chairperson’s Opening Remarks
Philip M. Arlen, M.D., President & CEO, Precision Biologics, Inc.
8:30 KEYNOTE PRESENTATION: Broad Coverage HLA-DR Subdominant Neoepitope-Based Cancer Vaccines
Keith Knutson, Ph.D., Director, Cancer Vaccine & Immune Therapies Program, Mayo Clinic
Vaccines that elicit helper T cells are effective in preventing tumor growth. Dominant class II epitopes drive tolerance through the generation of Tregs. There is a T cell repertoire to subdominant epitopes, the latter of which are presented during aberrant protein expression such as in tumors. We have developed pathways for identifying subdominant class II epitopes that bind promiscuously to HLA-DR molecules, establishing broad coverage helper T cell-inducing cancer vaccines.
9:00 Leveraging the Neo-Repertoire of Tumor-Specific Th1 Epitopes for Multiantigen Cancer Vaccines
William Watt, Ph.D., President & CEO, EpiThany
The “right” epitope in a tumor antigen can anchor an effective immune response and a tailored combination immunotherapy. Mutated neo-epitopes arise stochastically in some cancers and can be captured in real time as a tumor grows. EpiThany leverages epitopes that arise via the over-expression of established tumor antigens. By selecting antigens a priori and predicting epitopes in silico, we produce off-the-shelf vaccines against multiple antigens specific for the targeted tumors.
9:30 Comprehensive Profiling of T Cell Responses to Putative Neoantigens Reveals Smarter Targets for Cancer Immunotherapy
Theresa Zhang, Ph.D., Vice President, Personalized Cancer Vaccines, Genocea Biosciences
ATLAS is a high throughput, ex vivo platform that industrializes T cell response profiling. It enables unbiased, comprehensive identification of antigens for both CD8+ and CD4+ T cells in any patients regardless of their HLA genotypes. Case studies will be discussed where ATLAS is utilized to identify the right T cell antigens for better neoantigen vaccine and to profile T cell response that could predict efficacy of checkpoint blockade therapy.
10:00 Coffee Break
10:30 Discovery and Development of Novel Immunogenic Tumor Neoantigens for the Treatment of Solid Tumors
Philip 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. Neoantigens were identified in colon cancer with these functional antibodies.
11:00 Neoantigen Identification by Human Tumor Immunopeptidomics, NGS, and Deep Learning
Roman Yelensky, Ph.D., CTO, Gritstone Oncology
Genetic instability is a hallmark of cancer and, consequently, each cancer patient's tumor genome is different from their normal cells. This DNA difference leads to the creation of new protein antigens that are specific to tumor cells. These new antigens, known as tumor-specific neoantigens, can be recognized and targeted by the immune system. Gritstone Oncology is exploiting this vulnerability of tumor cells by identifying a patient's unique set of tumor antigens and deploying them in a therapeutic immunization strategy. Current approaches to neoantigen prediction from genomic sequence are limited in specificity and sensitivity. To build a best-in-class neoantigen prediction model, Gritstone collected large numbers of human tumors (initial focus on NSCLC) and characterized them by next-generation sequencing and HLA immunopeptidomics to measure HLA presented peptides. These data were used to build a neural network-based neoantigen prediction model that performs with high positive predictive value and offers broad HLA allelic coverage. Predicted neoantigens were further validated with in vitro T cell priming in HLA-matched systems.
11:30 High-Throughput Functional Screening of Neoantigens for Vaccines and TCR-Based Adoptive T Cell Therapies
Dolores J. Schendel, Ph.D., CEO & CSO, Medigene AG
Neoantigens are an important class of highly specific target molecules for various immunotherapies. In transiting from identification of mutant peptides by NGS and prediction of binding to HLA allotypes, Medigene explores high throughput technologies to functionally verify that predicted neoantigens do in fact lead to T cell recognition. Our rapid methods bypass the need for patient cells, overcoming logistical restrictions for determining the true immunogenicity of predicted neoantigens.
12:00 pm Close of Personalized Cancer Vaccines and Neoantigen Targeted Therapies