Cambridge Healthtech Institute’s Inaugural
Intrinsic and Acquired Resistance to Immunotherapy
Immuno-Oncology Therapeutic Strategies and Predictive Biomarkers for Non-Responders
June 12-13, 2018 | Westin Boston Waterfront | Boston, MA
Advances in immunotherapy, especially immune checkpoint blockade, continue to transform the treatment of certain cancers. However, when used as a monotherapy, many patients do not respond to treatment because of intrinsic, or innate, resistance. Others may respond initially but later develop acquired resistance. CHI’s Inaugural Intrinsic and Acquired Resistance to Immunotherapy meeting will focus on the mechanisms of resistance, the role of epigenetics and the tumor microenvironment in immune evasion, and the importance of longitudinal tumor sampling to discover biomarkers of response. Experts in the field of immunotherapy will present predictive and therapeutic strategies for overcoming resistance and improving patient outcomes.
Final Agenda
Tuesday, June 12
1:00 pm Conference Registration
1:55 Chairperson’s Opening Remarks
Pawel Kalinski, MD, PhD, Professor, Oncology; Vice-Chair, Translational Research, Roswell Park Cancer Institute
2:00 Genomic Signatures for Precision Immuno-Oncology
Iman Tavassoly, MD, PhD, Research Fellow, Mount Sinai Institute for Systems Biomedicine, Icahn School of Medicine at Mount Sinai
Finding biomarkers for optimization of immunotherapy in cancer is of great importance. Genomic signatures of a patient's immune system and the tumor tissue and their interactions are key regulators of response to immunotherapy. I will present an integrative computational and mathematical framework to extract these genomic signatures and build a quantitative biomarker space which can be used for precision immunotherapy in cancer.
2:30 Acquired Resistance to Immune Modulation in Lung Cancer
Katerina Politi, PhD, Associate Professor, Pathology, Yale School of Medicine
Immune checkpoint inhibitors have transformed the treatment landscape for lung cancer. However, most patients whose tumors initially respond to treatment eventually develop drug resistance disease. Emerging data indicate that lung tumors can escape treatment with immune checkpoint inhibitors by altering HLA Class I antigen presentation. Insights into how HLA Class I antigen presentation is disrupted in immune checkpoint inhibitor resistant tumors is critical to finding strategies to overcome drug resistance.
3:00 Primary Resistance Mechanisms to Immunotherapy
Sanjeev Mariathasan, PhD, Senior Scientist, Oncology Biomarker Department, Genentech
3:30 Refreshment Break in the Exhibit Hall with Poster Viewing
4:25 Chairperson’s Remarks
Pawel Kalinski, MD, PhD, Professor, Oncology; Vice-Chair, Translational Research, Roswell Park Cancer Institute
4:30 COX2-PGE2-Orchestrated Secondary Suppression in the Course of Immunotherapy
Pawel Kalinski, MD, PhD, Professor, Oncology; Vice-Chair, Translational Research, Roswell Park Cancer Institute
Immune checkpoint inhibition (ICI) provided new effective treatment option for patients with many types of advanced cancer, but the majority of patients still show primary or secondary resistance to ICI. The effectiveness of ICI and many other forms of cancer immunotherapy is regulated at the level of tumor microenvironments (TME) by the balance between type-1 immune cells, such as CD8+ cytotoxic T cells (CTLs), Th1 and NK cells and suppressive cells, such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). We observed that the activation of CTLs or NK cells in TMEs of human cancers, results in a strong mobilization of “secondary” suppression, mediated by activated MDSCs and their production of COX2, IDO, and IL-10, which suppress CTL function.
5:00 Antigen Presentation Defects and Resistance to Checkpoint Inhibitor Therapy
Ryan J. Sullivan, MD, Assistant Professor, Hematology & Oncology, Massachusetts General Hospital; Assistant Professor, Medicine, Harvard Medical School
Immune checkpoint inhibitor therapy leads to durable responses in a significant minority of patients with solid tumors and may improve overall survival in select diseases. However, most patients will not benefit and a significant percentage of patients who do respond, will develop acquired resistance. Proper antigen presentation is critical for initial and ongoing tumor immunity, and impaired antigen presentation machinery is an important mechanism of both intrinsic and acquired resistance.
6:30 Dinner Short Course*
SC3: Multiplexed Analysis of Tumor Tissues Using Spatially Resolved and Quantitative Platforms
*Separate registration required
Wednesday, June 13
7:25 am Interactive 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.
8:25 Chairperson’s Remarks
Roy D. Baynes, MD, PhD, Senior Vice President and Head, Global Clinical Development; CMO, Merck Research Laboratories
8:30 PD-1 Antibody Therapy: Approaches to Primary Resistance
Roy D. Baynes, MD, PhD, Senior Vice President and Head, Global Clinical Development; CMO, Merck Research Laboratories
PD-1 antibody therapy has shown broad spectrum activity across an array of solid malignancies. Informative biology helped identify those cancer types for initial exploration. A majority of patients however appear to exhibit primary resistance to such therapy. Precision medicine approaches help identify those patients most likely to respond to monotherapy, those patients who should be considered for further clinical research and potentially suggest combination approaches to address primary resistance.
9:00 Intrinsic Resistance to Immune Checkpoint Therapy and Potential Approaches to Overcome Resistance in Genitourinary Malignancies
Jianjun Gao, MD, PhD, Assistant Professor, Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center
This presentation will focus on both genomic and tumor microenvironment resistance mechanisms of immune checkpoint therapy; rationale for designing combinational approaches to overcome resistance using genitourinary malignancies including prostate, kidney and bladder cancer as models; and preliminary data on some of these combination therapy clinical trials.
9:30 Combination Immunotherapy Strategies to Overcome Resistance to PD-1 Therapy
Osama Rahma, MD, Assistant Professor, Medicine, Dana-Farber Cancer Institute, Harvard Medical School
Primary and adaptive resistance to PD-1 therapy represents a major challenge in immunotherapy drug development. Primary resistance could be driven by a defect in antigen presentation or priming the T-cells while secondary resistance could be related to the co-expression of many immune checkpoints. This presentation will explore immunotherapy combination strategies to overcome both primary and secondary resistance.
10:00 Networking Coffee Break
10:30 Targeting Soluble TNF in Tumor Microenvironment (TME) to Reverse Resistance to Immunotherapy
Raymond Tesi, MD, President and CEO, Acting CMO, INmune Bio
Checkpoint inhibitors do not work in a majority of patients. The most important predictor of resistance to CPI is MDSC in blood and/or TME. MDSC requires TNF to proliferate. Selective elimination of soluble TNF (with preservation of trans-membrane TNF) in blood and TME will reverse the immunologic factors that cause resistance to CPI and other immunotherapies.
11:00 Targeting the DNA Damage Response to Enhance Immunotherapeutics
Timothy Yap, MD, PhD, Associate Professor, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center
DNA damage response agents, such as PARP inhibitors, are widely used in clinical oncology and exploit deficiencies in tumor DNA repair. Given the expanding role of immune checkpoint inhibitors in cancer medicine, the interaction of tumor DNA damage with the immune system has recently come into focus. It is now clear that the tumor DNA repair landscape has a key role in driving antitumor response to immune checkpoint blockade.
11:30 Investigating the Role of Innate Immunity in Adaptive Resistance to Cancer Immunotherapy
Brent A. Hanks, MD, PhD, Assistant Professor, Cancer Immunology/Immunotherapy, Duke Cancer Institute
We will explore recently identified mechanisms that cancers have evolved to suppress T cell-mediated immunity as an adaptive response to checkpoint inhibitor immunotherapy. Further discussion will address strategies to inhibit these mechanisms and augment the efficacy of currently available checkpoint inhibitor regimens.
12:00 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:25 Chairperson’s Remarks
1:30 Response and Resistance in CAR-T Therapy
Elena Orlando, PhD, Bioinformatics Investigator, Novartis Institutes for Biomedical Research
2:00 Molecular Determinants for Sensitivity and Resistance to Immunostimulatory Therapies in Cancer
Kurt Schalper, MD, PhD, Assistant Professor, Pathology and Medicine (Medical Oncology), Yale School of Medicine
2:30 Cancer Immunotherapy Biomarkers for Selection and Monitoring
Glen J. Weiss, MD, MBA, Clinical Associate Professor, University of Arizona College of Medicine, Phoenix
There are now multiple monoclonal antibody immunotherapies available for clinical use to treat advanced cancers. However, just a fraction of these patients experience an impressive durable response. How are these therapies selected and how is efficacy monitored? This lecture will highlight current data on biomarkers being used and evaluated for treatment selection and monitoring.
3:00 Close of Conference