Cambridge Healthtech Institute’s Inaugural
Biomarkers for Immuno-Oncology
Exploring Mechanisms of Predictive and Therapeutic Response
18-19 March 2019
Given the complexities in successfully modelling the heterogeneity of tumours and the human immune system preclinically, it is inherently difficult to develop accurate predictive biomarkers for cancer immunotherapy. Thankfully there is a significant effort
across academia and industry to do just this. Employing cutting edge techniques such as genomics, transcriptomics, proteomics and metabolomics, as well as looking into more discreet blood niches, such as circulating tumour cells and exosomes, might
just provide necessary the answers. At Cambridge Healthtech Institute’s Inaugural Biomarkers for Immuno-Oncology conference we will address this and more.
Final Agenda
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MONDAY 18 MARCH
Recommended Short Course*
9:30 – 12:30 SC1: The Tumour Microenvironment and Response to Cancer Immunotherapy - Detailed Agenda
*Separate registration required
12:30 Conference Registration
13:30 Organizer’s Welcome Remarks
Joel Hornby, BSc Hons, Conference Director, Cambridge Healthtech Institute
13:35 Chairperson’s Welcome Remarks
Helen Angell, BSc, PhD, MD, Principal Scientist, Translational Science, Oncology IMED Biotech Unit, AstraZeneca
13:45 FEATURED PRESENTATION: ctDNA as a Biomarker for Early Tumor Response Assessment in Lung Cancer Patients Treated with Immunotherapy
Ed Schuuring, MD, Head of the Laboratory of Molecular Pathology, Pathology, University Medical Center Groningen
A significant minority of patients treated with immune checkpoint inhibitors show durable responses, but no adequate biomarkers are available for predicting which patients will benefit. Immunotherapy is expensive and potentially toxic. Patient response
is monitored by tumor volume using CT scanning. The aim of our study is to assess plasma KRAS/BRAF-mutant levels as an early biomarker and a monitoring tool for durable responses to immunotherapy in KRAS/BRAF-mutated advanced NSCLC.
14:15 Integrative Cancer Immunology: Clinical Translation of IO Biomarkers and the Immunoscore
Helen Angell, BSc, PhD, MD, Principal Scientist, Translational Science, Oncology IMED Biotech Unit, AstraZeneca
The Immunoscore, based on the quantification of lymphocytes and cytotoxic T cells at the tumour centre and invasive margin, is a clinically useful prognostic marker in colorectal cancer. The mechanistic relationship between tumour infiltrating immune
cells and microsatellite instability will be presented. Translation of immune quantification into the clinic, evaluating additional indications and profiling the immune landscape of distinct molecular segments will be discussed.
14:45 Bim and Soluble PD-L1 as Biomarkers of Response to Anti-PD1 Therapy
Roxana Dronca, MD, Associate Professor of Oncology, Consultant and Chair, Division of Hematology-Oncology, Mayo Clinic
The dynamics and heterogeneity of programmed cell death protein ligand 1 (PD-L1) expression confound its use as a predictive biomarker in cancer immunotherapy, but blood-based biomarkers have the potential to predict responders and detect mechanisms
of resistance to immunotherapy. We report that measurements of T cell biomarkers (Bim and effector memory) and sPD-L1 levels provide a new non-invasive way to predict and monitor patient responses to anti-PD-1 monotherapy in melanoma and lung
cancers.
15:15 Networking Refreshment Break
15:45 Prognostic and Predictive Markers for Immunotherapy and Combination Therapy
Kathleen M. Mahoney, PhD, MD, Instructor of Medicine, Medicine, Hematology-Oncology, Beth Israel Deaconess Medical Center, Dana-Farber Cancer Institute
Many clinical trials have investigated the toxicity and efficacy of combining PD-1 pathway blockade with other therapies. Yet few randomized Phase II studies involving immune checkpoints have been designed to develop predictive biomarkers for these
therapies. Biomarker-driven early phase trials are needed for designing Phase III trials to prospective validate (protein or gene signature-based) biomarkers for monotherapy or combination immunotherapy, which is necessary for expediting patients’
access of these therapeutic options.
16:15 Next-Generation Biomarkers for the Era of Combination Cancer Immunotherapy
Mohini Rajasagi, PhD, MD, Director Translational Oncology and Clinical Biomarkers, Oncology Clinical Research, Merck Sharpe and Dohme (MSD)
Immune checkpoint blockade therapies are revolutionizing the standard of care for cancer treatment. However, not all patients respond to immunotherapy and even those that do, often experience toxicities. Combination approaches are the key to improving
clinical response. Novel biomarkers and high throughput technologies enable us to understand the mechanisms underlying the complex interactions between the immune system and cancer, identify predictive biomarkers for the patients who will
most likely benefit from current immunotherapies, avoid immune-related adverse events, mechanisms of resistance and guide future combination cancer immunotherapy.
16:45 Rapid High-Throughput Functional Selection of Neoantigens and Assessment of Their Safety
Milosevic Slavoljub, MD, Head of Technology and 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.
17:15 Concepts
of Biomarker use in Regulated Bioanalysis in Immuno-Oncology
Arno Kromminga, PhD, Senior Vice President & Global Chief Scientific Officer & Managing Director at BioAgilytix Europe,BioAgilytix
Increased understanding of
cellular and molecular mechanisms about the interactions between tumor
development and immunological reactions has resulted in increased activities to
treat cancer patients with immunological tools. These tools include the use of
check points inhibitors but also novel cellular constructs to enable the immune
system to recognize and eliminate tumor cells. Within this exciting field of
immune-oncology, it is desirable to identify and characterize patients to be
eligible for a specific treatment and to control the efficiency of a possible
treatment regimen during the treatment period. In regulated the bioanalysis the
regulatory requirements for biomarkers depend on the context of use (COU). As
the criteria for a biomarker and its COU are related to the level of risk
associated with dependence on the use of biomarker data to make decisions about
human health, the concepts of different levels of qualification/validation of
Biomarkers classes will be discussed.
17:35 From Staining to Analysis:
End-to-End Application of UltiMapper™ Kits for Multiplexed Immuno-Profiling
Angela Vasaturo, PhD,
Senior Field Application Scientist, Ultivue
Learn how UltiMapper multiplex IHC assays enable access to whole-slide, highly multiplexed biomarker data optimized on the Leica BOND RX autostainer and analyzed using HALO image analysis software.
17:45 Welcome Reception in the Exhibit Hall with Poster Viewing
18:45 Close of Day
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TUESDAY 19 MARCH
8:00 Registration and Morning Coffee
8:30 Chairperson’s Opening Remarks
Graham Pawelec, MA, PhD, FGSA, Professor of Experimental Immunology, Second Department of Internal Medicine, University of Tuebingen Clinical School, Germany; Affiliated Scientist, Cancer Solutions Program, Health Sciences North Research Institute,
Canada
8:35 Aging and the Human Immune System in the Era of Immunomodulatory Antibody Therapy for Cancer: Is It All Downhill?
Graham Pawelec, MA, PhD, FGSA, Professor of Experimental Immunology, Second Department of Internal Medicine, University of Tuebingen Clinical School,
Germany; Affiliated Scientist, Cancer Solutions Program, Health Sciences North Research Institute, Canada
It is “common knowledge” that the human immune system deteriorates over time, resulting in an increased frequency of and susceptibility to infectious disease, autoimmunity and cancer, and in poorer responses to vaccines in the
elderly (immunosenescence). This presentation will consider the clinically highly relevant question of the impact of immune aging on the responses of cancer patients to immunomodulatory antibody therapy that is currently revolutionizing
medical oncology (2018 Nobel Prize).
9:05 Immune-Stroma-Tumor Cell Interactions in Understanding Immune Blockade Drug Response
Jun Zhu, PhD, Professor, Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai and Sema4, a Mount Sinai venture
Immune cell infiltration is positively associated with immune blockade drug response in general. However, high proportion of immune cell infiltration may not necessarily lead to good immune blockade drug response. We recently showed that immune
and stroma cell interaction can predict PD-L1 response in bladder cancer (Wang et al, Nature Communications, 2018). Our single cell sequencing and computational modeling provide further insights of how immune-stroma-tumor cell interactions
can determine immune blockade drug response.
9:35 Problem Solving Roundtable Discussion
Prognostic Biomarkers for Melanoma Patients
Moderator: Vivian Barak, PhD, Prof, Head, Immunology Lab for Tumor Diagnosis, Oncology, HADASSAH-Medical Center
Biomarkers to Predict Response and Toxicity to Immunotherapy
Moderator: Roxana Dronca, MD, Associate Professor of Oncology, Consultant and Chair, Division of Hematology-Oncology, Mayo Clinic
Developing Biomarkers for Combination Therapy
Moderator: Kathleen M. Mahoney, PhD, MD, Instructor of Medicine, Medicine, Hematology-Oncology, Beth Israel Deaconess Medical Center, Dana-Farber Cancer
The Value of Liquid Biopsy as a Non- or Minimally Invasive Approach for Diagnostics and Therapy Monitoring
Moderator: Irina Nazarenko, PhD, Group Leader, Exosome and Tumor Biology, Medical Center, University of Freiburg
10:35 Coffee Break in the Exhibit Hall with Poster Viewing
11:15 Systems Approach to Cancer Immunology Biomarker Discovery
Matthew Albert, MD, PhD, Principal Scientist, Cancer Immunology, Genentech
Germline genetic polymorphisms influence tumor gene expression and immune cell infiltration.
11:45 Applying Immune Receptor Sequencing in the Discovery and Profiling of Immuno-Oncology ‘Living Drugs’
Jan H. Bergmann, PhD, Senior Scientist, Genomics Platform Technologies and Immune Receptor Discovery, AgenTus Therapeutics
Recent developments in sequencing technologies both on bulk and in particular the single cell level open up tremendous opportunities in functional immune receptor discovery, preclinical R&D as well as treatment monitoring in the field
of immuno-oncology. Collectively, genomics technologies paired with innovative cell and molecular strategies are leveraging increased sensitivity and specificity to complement this rapidly developing therapeutic field.
12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
12:45 Dessert Break in the Exhibit Hall with Poster Viewing
13:15 Session Break
14:00 Chairperson’s Remarks
Tina J. Hieken, MD, FACS, Associate Professor of Surgery, Surgery, Mayo Clinic
14:05 The Breast Tissue Microbiome, Stroma and Immune Cells in Association with Benign and Malignant Breast Disease
Tina J. Hieken, MD, FACS, Associate Professor of Surgery, Surgery, Mayo Clinic
Stromal changes, as well as alterations in the immune cell composition of benign breast lobules, encompassing both innate and adaptive immune effectors, have been described in association with future breast cancer risk. In tandem, pilot data
suggests that the composition of the innate microbiome of sterilely obtained histologically normal breast tissues is different between women with and without breast cancer. Associations between the breast tissue microbiome, microenvironment
and disease state (benign versus malignant) suggest potential novel biomarkers of breast cancer risk and targets for primary prevention.
14:35 Relevance of Heterogeneous EV Populations for Liquid Biopsy as a Source of Biomarkers
Irina Nazarenko, PhD, Group Leader, Exosome and Tumor Biology, Medical Center, University of Freiburg
The need to develop better approaches allowing comprehensive molecular characterization of a progressing tumor has led to the development of the “Liquid Biopsy” concept. In view on the complexity of blood and availability of components
of different origins, a question of a specific impact of each of these different compartments, such as free circulating nucleic acids and extracellular vesicles on the outcome of liquid biopsy-based diagnostic can be addressed.
15:05 The Power of Single Molecule Imaging in IO Biomarker Discovery and Target Engagement Studies
Mariya Georgieva, PhD, Head of Business Development and Imaging, ONI
Quantitative imaging techniques are powerful tools enhancing the predictability and reliability of pre-clinical models for drug discovery and target validation. ONI crafts bench-top instruments with single-molecule sensitivity allowing the direct observation and measurement of molecular interactions, cellular dynamics, and complex tissue phenotypes.
15:35 Refreshment Break in the Exhibit Hall with Poster Viewing
16:15 A Significant Clinical Role of the Immune Biomarker sIL-2R for Cancer Patients
Vivian Barak, PhD, Prof,
Head, Immunology Lab for Tumor Diagnosis, Oncology, HADASSAH-Medical Center
sIL-2R is an Immune Biomarker and its blood levels can be used in Various Malignancies to; distinguish between Cancer patients and normal controls, distinguish between subgroups of patients (with or without metastases, active vs non-active disease ), evaluate therapy effects, provide prognosis for patients, I intend to present our results for patients with Breast Cancer, Melanoma-both Cutaneous and Uveal, Head and Neck Cancer, etc., our results are in concordance with other studies performed all over the world. In conclusion, sIL-2R is a sensitive and reliable Immune Biomarker and should be used routinely in Oncology.
16:45 The First Biomarker-Defined Tumor Indication: FDA Approval of Pembrolizumab for MSI-High Cancer
Kenneth Emancipator, DABP, MD, Executive Medical Director and Head of Companion Diagnostics, Translational Medicine, Merck & Co.
The program presents an overview of microsatellite instability (MSI) and mismatch repair defect (dMMR), and how it fits into the tumor immunogenicity-inflammation pathway. It reviews the history and clinical evidence for MSI and dMMR as a
predictive biomarker for response to pembrolizumab. It discusses the unprecedented – and unorthodox – path to FDA approval of pembrolizumab. Finally, it discusses MSI and dMMR in the broader context of biomarkers in immuno-oncology.
17:15 Multiplexing of Tryptophan and Its Metabolites for Patient Stratification and Monitoring in Immuno-Oncology
Christiane Opitz, PhD, Group Leader, Brain Cancer Metabolism, German Cancer Research Center, DKFZ
Tryptophan degradation is a potent immunosuppressive mechanism regulating anti-tumor immune responses. As treatments modulating tryptophan degradation are becoming available, methods to efficiently and precisely measure tryptophan degradation
are becoming increasingly relevant both for stratification of patients to treatments as well as assessment of therapeutic efficacy. We employed isobaric mass tags to develop a method that enables quantitative comparison of tryptophan
degradation simultaneously in up to 11 different samples. Using this method we studied the effects of the tryptophan pathway modulator indoximod on tryptophan metabolism in human cancer and immune cells. A proof of principle study
comparing tryptophan degradation in 40 glioblastoma patients to age- and sex-matched healthy controls revealed reduced levels of tryptophan and downstream tryptophan metabolites in the glioblastoma patients.
17:45 Close of Biomarkers for Immuno-Oncology
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