Cambridge Healthtech Institute’s Third Annual
Biomarkers for Cancer Immunotherapy and Combinations
Immunopheno- and Genotyping to Define Tumor-Immune Interactions
August 15-16, 2017 | Grand Hyatt Washington | Washington, DC
The heterogeneity of cancer, and the complexity of cancer and immune cells interaction require sophisticated phenotypic and genotypic cell analysis in order to answer important questions in the course of new immuno-oncology (IO) agents discovery and clinical development. Flow cytometry and its variations became instrumental for immunophenotyping, single cell analysis and identification of functional biomarkers of tumor-immune interactions. In turn, next generation sequencing is playing an important role in neoantigens research. Another important goal for IO biomarker quest is design of multiplex biomarkers to guide combination cancer therapy. Cambridge Healthtech Institute’s 3rd Annual Biomarkers for Cancer Immunotherapy and Combinations is designed to feature cutting edge diagnostics technologies and their applications for new IO biomarker identification and validation.
Final Agenda
Recommended Short Course(s)*
SC9: Genomics in the Service of Cancer Immunotherapy - Connecting DNA Repair, Mutational Processes and Genotoxic Therapy to Successful Cancer Immunotherapy
*Separate registration required
TUESDAY, AUGUST 15
7:30 am Main Conference Registration & Morning Coffee
8:30 Chairperson’s Opening Remarks
Anka G. Ehrhardt, Ph.D., Director, Clinical Cytometry, Translational Medicine, BMS
8:40 Developing ‘Next-Gen’ Cell-Based Cancer Immunotherapies
Nicholas P. Restifo, M.D., Principal Investigator, National Cancer Institute, NIH
Our work focuses on immunotherapy based on the adoptive transfer of naturally-occurring and gene-engineered tumor-specific T cells. New cell-based immunotherapies for patients with advanced cancer can be effective, but need continual improvement. This iterative process involves close collaboration with basic researchers, biotech scientists and experimental clinicians. We will discuss the signals that T cells receive within tumor masses, and what T cells must do to trigger the eradication of tumor cells.
9:15 Natural Variation in Innate Immune Cell Parameters Is Driven by Genetic Factors
Matthew Albert, Ph.D., Principal Scientist, Cancer Immunology, Genentech
Enumeration and characterization of circulating immune cell populations provide key indicators of human health and disease. To identify environmental and genetic factors driving innate and adaptive immune cell parameters in homeostatic conditions, we combined semi-automated flow cytometric analysis of blood leukocytes and genome-wide DNA genotyping in 1,000 healthy, unrelated individuals of western European ancestry. We established age and latent CMV infection as major and independent factors modulating T cell populations and impacting the frequency of differentiated memory cells, and show that active smoking correlates with increased levels of Treg and decreased numbers of mucosal associated innate cells (MAIT). Genome-wide association study of the 168 measured immunophenotypes detects 14 independent loci, of which 11 are newly identified. Using these results, we established models that quantify the respective contribution of identified genetic and non-genetic factors in controlling homeostasis of circulating white blood cells in healthy individuals. We observed a stronger impact of genetic factors on innate cell phenotypes, as compared to adaptive immune cells, suggesting that potential genetic control of the adaptive immune system is obscured by life-long environmental exposures. Implementation of key non-genetic and genetic determinants may improve diagnostic criteria and further the utility of cell phenotype laboratory measurements in the ultimate development of personalized strategies for patient management in the clinical setting.
9:50Experimental Data Driven and Computational Improvements of Cancer Neoepitope Prediction
Zoltan Szallasi, Ph.D., M.D., Senior Research Scientist, Children’s Hospital Informatics Program, Children’s Hospital Boston, Harvard Medical School; Assistant Professor, Pediatrics, Harvard Medical School; Assistant Professor, Pediatrics, Boston Children’s Hospital
10:10 Coffee Break in the Exhibit Hall with Poster Viewing
10:55 Chairperson’s Remarks
Chris Meda, Chief Business Officer, IncellDx, Inc.
11:00 What Does It Take to Make Flow Cytometry a Routine Assay in the Clinic and as PDx?
Anka G. Ehrhardt, Ph.D., Director, Clinical Cytometry, Translational Medicine, BMS
Today, immuno-oncology is one of the most competitive fields in pharmaceutical research, and with its power to characterize the status of the immune system, flow cytometry is a key technology in evaluating the immune status of a patient, and changes in response to treatment. Flow cytometry is traditionally a method between science and art, suited for discovery work, useful in pre-clinical work, and difficult in clinical studies. With fast new developments in the technologies used in flow cytometry, the road is open to shape flow cytometry to overcome the typical challenges in the clinic (most notably, sample stability and assay reproducibility). This presentation will outline a strategy using the power of simple tools (such as selecting the right blood collection tube, standardization and normalization) and disruptive new technologies for point-of-care walk-away sample analysis in bringing flow cytometry assays up to the level of robustness required under real-life conditions.
11:30 Monitoring Minimal Residual Disease in Acute Leukemia: Technical Challenges and Interpretive Complexities
Brent Wood, M.D., Ph.D., Professor, Laboratory Medicine and Pathology, Director, Hematopathology Laboratory and SCCA Pathology, Medical Director, SCCA Laboratories, University of Washington
The detection of residual disease following therapy is rapidly becoming standard of care in the management of patients with acute leukemia. The methodology, clinical significance and limitations of minimal residual disease testing by flow cytometry and next-generation sequencing will be presented.
12:00 Single Cell, Multiplex, Protein, mRNA Quantification Using Flow Cytometry: Clinical Apps in Oncology and Immune-Oncology
Bruce Patterson, Ph.D., CA CEO, Co-Founder, Executive, IncellDx
Chris Meda, Chief Business Officer, Executive, IncellDx
IncellDx’s Cellular Multiplex™, a quantitative, flow cytometric diagnostic approach, that allows multiplexing of proteins using antibodies, mRNA by in situ hybridization, and DNA cell cycle. Morphologic measurements can be determined as well providing a multi-parameter, quantitative alternative to IHC.
12:30 pm Q & A with Speakers of Session
1:00 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:30 Refreshment and Cookie Break in the Exhibit Hall with Poster Viewing
2:00 Chairperson’s Remarks
Ashley Cimino-Mathews, M.D., Associate Professor of Pathology and Oncology, The Johns Hopkins Hospital
2:05 Modeling the Cyber War between the Immune System and Tumor Cells
Sam M. Hanash, M.D., Ph.D., Professor, Molecular Pathology, Division of Pathology/Lab Medicine, The University of Texas MD Anderson Cancer Center
This presentation will review progress toward elucidating the diverse mechanisms through which tumor cells evade immune monitoring.
2:35 Tissue Phenomic Approaches in the Study of Biomarkers of Tumor-Immune Cellular Interactions
Marlon C. Rebelatto, D.V.M., Ph.D., Dipl. ACVP, Principal Pathologist, Translational Sciences, MedImmune
A significant proportion of patients do not respond to monotherapies and combination therapies in development have so far provided only marginal improvements and with additional toxicities. The identification of the right patients for the right therapy continues to be an essential aspect of drug development. With greater understanding of biology, scientists may be able to narrow the list of candidate biomarkers that relate to the mechanism of action of a given drug or the biology being targeted. In this presentation, we describe Tissue Phenomic approaches to study biomarkers of tumor-immune cellular interactions.
3:05 Characterizing and Targeting the Breast Tumor Microenvironment
Ashley Cimino-Mathews, M.D., Associate Professor of Pathology and Oncology, The Johns Hopkins Hospital
The immune microenvironment has an important role in breast cancer progression and response to therapy. Key components of the breast tumor microenvironment are tumor infiltrating lymphocytes and cellular expression of checkpoint inhibitor proteins, particularly PD-L1/PD-1. An active immune microenvironment is seen across the spectrum of breast cancer progression, from in situ to invasive and metastatic disease, and unique microenvironment components are seen in special subtypes of invasive carcinoma.
3:35 IO Biomarker Discovery Strategies to Maximize Information from the Tumor Microenvironment in Limiting & Diverse Samples
Jarret Glasscock, Ph.D., CEO, Cofactor Genomics
A number of complimentary approaches to characterize the tumor microenvironment have emerged over recent years. These include quantification of immune cell subtypes, monitoring expression levels of immune checkpoint genes, measuring mutational burden, T-cell repertoire characterization, and spatial information. In an effort to do more in IO biomarker discovery with less, we will present recent results on ambitious efforts to expand the application of these approaches to diverse sample types with limited sample quantity and quality.
4:05 Refreshment Break in the Exhibit Hall with Poster Viewing
4:50 Integration of Biomarkers for Prediction of Response to Anti-Cancer
Kurt A. Schalper, Ph.D., Assistant Professor, Pathology and Medicine (Medical Oncology), Yale University
Immune checkpoint blockers have emerged as effective anti-cancer agents in various tumor types. Predictive biomarkers have been described, but their clinical use is limited by their variable performance and restricted understanding of their biological significance. Numerous trials using combinations of immune and non-immune agents are ongoing and could impact the use of biomarkers to monitor and predict responses. Here, we will discuss the current and future landscape of immunotherapy biomarkers focusing on their potential for integration in lung cancer.
5:20 PANEL DISCUSSION: Defining Tumor-Immune Interactions
Kurt A. Schalper, Ph.D., Assistant Professor, Pathology and Medicine (Medical Oncology), Yale University
Panelists: Alan L. Epstein, M.D., Ph.D., Professor, Pathology, Keck School of Medicine, University of Southern California
Marlon C. Rebelatto, D.V.M., Ph.D., Dipl. ACVP, Principal Pathologist, Translational Sciences, MedImmune
Sam M. Hanash, M.D., Ph.D., Professor, Molecular Pathology, Division of Pathology/Lab Medicine, The University of Texas MD Anderson Cancer Center
5:50 Wine & Cheese Pairing Welcome Reception in the Exhibit Hall with Poster Viewing
6:50 Close of Day
WEDNESDAY, AUGUST 16
7:15 am Registration
7:30 Problem-Solving Breakout Discussions with Continental Breakfast
The Tumor Microenvironment
Moderator: Ashley Cimino-Mathews, M.D., Associate Professor of Pathology and Oncology, The Johns Hopkins Hospital
- The role of tumor infiltrating lymphocytes as a prognostic and predictive biomarker
- The role of ER and HER2 in patient selection for checkpoint inhibitor therapy in breast cancer
- The challenges in PD-L1/PD-1 assay selection and implementation
Biomarkers and Diagnostics to Support Clinical Trials in IO
Moderator: Robert A. Anders, M.D., Ph.D., Associate Professor of Pathology, Division of GI and Liver Pathology, Bloomberg-Kimmel Institute for Cancer Immune Therapy, Johns Hopkins Medicine
- Biomarker standardization
- Biospecimen handling for immuno-oncology studies
- Who do we need to partner with to be successful?
- Future of immuno-oncology studies, novel approaches and platforms
8:25 Chairperson’s Opening Remarks
Robert A. Anders, M.D., Ph.D., Associate Professor of Pathology, Division of GI and Liver Pathology, Bloomberg-Kimmel Institute for Cancer Immune Therapy, Johns Hopkins Medicine
8:30 The Genomic and Immunologic Determinants of Response to Head and Neck Cancer Immunotherapy
Rajarsi Mandal, M.D., Head and Neck Surgical Oncology Fellow, Department of Surgery, Memorial Sloan Kettering Cancer Center
Immune checkpoint blockade is a promising approach for the treatment of human malignancies and has led to improved response rates and durable clinical benefit in a subset of patients. However, the extent to which patients derive benefit is diverse and the determinants of response to therapy are ill-defined. We have sought to define the genomic and immunologic determinants of response to immune checkpoint blockade therapies such as anti-CTLA-4 and anti-PD-1. Our work has shown that tumor mutational burden, clonality, and the tumor immune landscape help dictate clinical response to immune-based therapies.
9:00 The MDSC Clinical Assay for the Immunodiagnosis and Monitoring of Solid Tumors
Alan L. Epstein, M.D., Ph.D., Professor, Pathology, Keck School of Medicine, University of Southern California
Myeloid Derived Suppressor Cells (MDSC) are a recently identified subset of suppressor cells which are induced by and recruited to the tumor microenvironment to suppress immune activation of cytotoxic T cells. Our laboratory has developed a three antibody panel to quantify these cells by flow cytometry in order to study their relationship to malignancy and tumor volume. To date, blood samples from patients with 4 solid tumor types have been analyzed which demonstrate the clinical potential of MDSC to diagnose and monitor tumor growth and recurrence.
9:30 How to Improve Predictive Biomarkers: Lessons Learned from Immune Therapy in Colorectal Cancer
Robert A. Anders, M.D., Ph.D., Associate Professor of Pathology, Division of GI and Liver Pathology, Bloomberg-Kimmel Institute for Cancer Immune Therapy, Johns Hopkins Medicine
PD-L1 expression has been touted as a predictive biomarker for immune therapy. While PD-L1 expression does have some predictive power, it is not a perfect biomarker. Biomarkers that integrate genomic, protein and immunologic markers may have better predictive power. When this strategy is applied to patients with colorectal cancer, it is possible to select over 90% of patients that are likely to show a biologic response to anti-PD-1/L1 therapy.
10:00 Multimodal Biomarker Testing for Immunotherapy Applications
Meredith Berry, Ph.D., Director, Laboratory Operations and Pharma Services, Laboratory Operations and Pharma Services, NeoGenomics
PD-L1 remains the most extensively used biomarker in immunotherapy. New molecular biomarkers, including tumor mutation burden and microsatellite instability, are emerging as potential predictors of immunotherapy response. Selecting biomarkers that predict efficacy of combined immuno/targeted therapy is a significant unmet need. Data correlating genomic biomarkers with PD-L1 will be presented.
10:30 Coffee Break in the Exhibit Hall with Poster Viewing
1:05 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:35 Ice Cream and Cookie Break in the Exhibit Hall with Poster Viewing
1:35 Close of Biomarkers for Cancer Immunotherapy and Combinations