As rapid development of novel immunotherapies continues, there is enormous pressure to discover and validate relevant biomarkers. Cambridge Healthtech Institute’s Inaugural Biomarkers for Immunotherapy conference has been designed to support a coordinated
effort by industry players to discover biomarkers that will enable commercial immunotherapies and immunotherapy combinations through clinical development and into the market. Key focus will be given to combination therapies, biomarkers beyond PD-1,
and ensuring safety. Overall, this event will provide solutions and strategies for integrating immunotherapies into the precision medicine model.
WEDNESDAY, 12 APRIL
13:30 Chairperson’s Opening Remarks
Shao-An Xue, Ph.D., Genetic Engineering Laboratory, School of Biological & Environmental Engineering, Xi’an University, Institute of Immunity & Transplantation, University College London Medical School, United Kingdom
13:35 Cytomegalovirus and Epstein-Barr Virus, Two Unique Biomarkers for Immunotherapy of the Virally Associated Malignancies
Shao-An Xue, Ph.D., Genetic Engineering Laboratory, School of Biological & Environmental Engineering,
Xi’an University, Institute of Immunity & Transplantation, University College London Medical School, United Kingdom
Using CMV and EBV as biomarkers, we isolated HLA-A2-restricted TCR genes specific for CMV and EBV, and retrovirally transduced them into human T cells, thus generated MHC class I-restricted both CD8+ and CD4+ T cells specific
for these viruses. This talk will describe a robust approach for generating CD8+ CTL and CD4+ Th cells capable of providing MHC class I-restricted antitumor immunity by targeting CMV and EBV as biomarkers.
14:05 Biomarkers for Early Phase Immune-Oncology Trials
Sid Katugampola, Ph.D., Biomarker & Translational Scientist, Centre for Drug
Development, Cancer Research UK, United Kingdom
Numbers of immunotherapeutic anti-cancer therapies are on the rise and these are showing promising anti-tumour efficacy. Successful translation of these agents and understanding if and how these would work clinically, particularly for first in class (FIC),
are of great importance. The use of pharmacodynamic biomarkers in early phase clinical development for such FIC agents provide exciting opportunities but also significant challenges in trials done on late stage cancer patients.
14:35 PD-L1 Expression in HPV Related Cancer: A Multiparameter Biomarker Approach
Ekaterina S. Jordanova, Ph.D., Principle Investigator, Obstetrics and Gynaecology,
Centre for Gynaecological Oncology Amsterdam, The Netherlands
Expression of PD-L1 is still a controversial biomarker for selecting patients for PD1/PD-L1 checkpoint inhibitor immunotherapy. In virally induced tumours such as cervical-, penile-, vulvar-, and head-and-neck cancer various immunotherapy clinical trials
are being currently planned or performed. We have recently reported on the link between PD-L1 expression in cervical-, penile- and head-and-neck cancer with poor prognosis. We have developed a multiparameter immunofluorescent technique allowing the
analysis of PD-L1 expression in combination with other crucial immune-microenvironment markers. Conceivably, in the near future patients might be easily stratified for particular personalized immunotherapies based on comparable approaches.
15:15 Refreshment Break in the Exhibit Hall with Poster Viewing
16:15 KEYNOTE PRESENTATION: Precision Immunotherapy: The Challenge of Converting Complex Predictive Biomarkers into Practical Companion Diagnostics
Kenneth Emancipator M.D., Executive Medical Director, Translational Medicine, Companion
Diagnostics, Merck & Co., United States
Early immunotherapies have produced dramatic results for some patients, but future immunotherapies likely need to be guided by diagnostics to benefit more patients. Properly targeting immunotherapy requires incorporating into clinical practice complex
diagnostics which can assess host immune response in addition to cancer biology itself. “Precision Immunotherapy” requires discovery of appropriate predictive biomarkers and incorporating them into practical companion diagnostics which
will be adopted by practitioners.
16:45 Immunostimulatory and Oncolytic Properties of Rotavirus Can Overcome Resistance to Immune Checkpoint Blockade Therapy.
Tala Shekarian, Targeting of Tumor and It's Immune Environments, Lyon Cancer Center, France
Oncolytic properties of viruses can be exploited for the priming of anti-tumor immune responses. We have found that commercially available rotavirus vaccines do have oncolytic properties. This attenuated virus can directly kill cancer cells. They have
pro-inflammatory properties and activate the NF-Kb pathway in a toll-like receptor and IRF3 independent manner. Interestingly, in immunocompetent murine tumor models, intra-tumoral rotavirus overcome resistance and synergize with immune checkpoint
17:15 Engineering 2nd Generation SPEAR™-T Cells to Overcome TGF-β-Mediated Immunosuppression for Adoptive Cell Therapy
Jonathan Silk, Ph.D., Group Leader, Cellular Biology, Adaptimmune Ltd, United Kingdom
Adoptive Cell therapy with NY-ESO SPEAR-T cells, is showing promising initial clinical responses in clinical trials for solid and liquid tumors. However, the depth and durability of responses may be affected by inhibitory cytokines such as Transforming
Growth Factor-β (TGF-β). We investigated whether SPEAR-T cells engineered to express a dominant negative TGF-β receptor (dnTGFβRII) were resistant to the inhibitory effects of TGF-β in vitro.
17:45 Close of Day
THURSDAY, 13 APRIL
08:30 Registration and Morning Coffee
09:00 Chairperson’s Remarks
Thomas O. Kleen, Ph.D., Executive Vice President, Immune Monitoring, Epiontis GmbH, Germany
09:05 Next-Generation Immune Monitoring Tools for Immuno-Oncology Trials and Biomarker Discovery- Reducing Sample Amounts and Simplifying Logistics
O. Kleen, Ph.D., Executive Vice President, Immune Monitoring, Epiontis GmbH, Germany
Current and next generation Immunotherapy trials now can be monitored with epigenetic-based, quantitative real-time PCR assisted cell counting (qPACC). Samples can be simply frozen and easily shipped without burden on clinical sites, allowing
precise and robust quantification of immune cells in all human samples from only 75ul-250ul of whole blood or small amounts of tissue. Regulatory T cells (Tregs), Th17, Tfh, CD3+, CD4+, CD8+, B, NK and PD-1 positive cells are the first examples
of a next generation tools for immune monitoring immuno-oncology trials and biomarker discovery.
09:35 Profiling of Immunity Biomarkers in Whole Blood
Alex Chenchik, Ph.D., Scientific Director, Cellecta, Inc., United States
For unbiased discovery of predictive and prognostic biomarkers, we have developed a targeted RNA expression assay that profiles 19,000 genes based on multiplex RT-PCR followed by NGS in whole blood samples stabilized in PAXgene. In this study,
we present the performance of the assay for immunophenotyping of immune cells in blood samples from TNBC and sepsis patients and assess the immune responses to complex immunomodulatory stimuli in ex vivo model system.
10:05 Post Translationally Modified Auto-Antigens a Biomarker For Early Diagnosis of Autoimmune Disease
Ahuva Nissim, Reader, Antibody and Therapeutic Engineering, Biochemical Pharmacology, Queen
Mary University, United Kingdom
Oxidative stress might be a critical player in the parthenogenesis of inflammatory autoimmune diseases. This include Rheumatoid arthritis and type 1 diabetes. Our data shows that in both disease the tissue specific auto-antigens are infect auto-antigens
that have been post-translationally modified by oxidants present in the diseased tissue. We have shown specific reactivity to oxidated collagen type II and insulin in rheumatoid arthritis and type 1 autoimmune diabetes, respectively.
10:35 Coffee Break in the Exhibit Hall with Poster Viewing
11:20 Loss of Immune Recognition by Aberrant Expression of HLA Class I Antigens in Tumors
Barbara Seliger, Ph.D., Professor and Director, Medical Immunology, Martin
Luther University Halle-Wittenberg, Germany
MHC class I abnormalities occur in a high frequency of tumors of distinct origin and are often associated with worse prognosis and reduced patients’ survival. The underlying molecular mechanism of these deficiencies are diverse and include
total, haplotype, allelic loss or downregulation of HLA class surface antigens, or deregulation of major components of component of the MHC class I antigen processing machinery mediated by either transcriptional, epigenetic or posttranscriptional
11:50 Monitoring Immune Dysfunction in the Leukemia Microenvironment
Sergio Rutella, M.D., Ph.D., Professor, Cancer Immunotherapy, John van Geest
Cancer Research Centre, College of Science and Technology, Nottingham Trent University, United Kingdom
Escape from immune surveillance is a hallmark of cancer. The dysfunction of T cells, NK cells and dendritic cells (DC) contribute to defective anti-leukemia responses. IFN-γ-inducible targets expressed by tumor and/or microenvironmental
cells, such as indoleamine 2,3-dioxygenase-1, arginase-II, HLA-G and PD-L1, favour T-cell suppression, inhibition of NK-cell function and DC maturation arrest. Strategies are being developed to tackle the above immune suppressive circuits
with the aim to improve clinical outcome.
12:20 Sponsored Presentation (Opportunity Available)
12:50 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
13:20 Session Break
14:20 Chairperson’s Remarks
Dirk Brockstedt, Ph.D., Senior Vice President, R&D, Aduro BioTech Inc., United States
14:25 Anticipating, Detecting and Treating Immune-Related Toxicity: A Challenge for Combinatorial Immunotherapy
Ioannis Karydis, Ph.D., Associate Professor, Oncology, Cancer Sciences, University
of Southampton, United Kingdom
Tumour immunotherapy is coming of age, with a rising number of agents gaining regulatory approval. However, in most cases single agent response rates remain typically well below 40%. Combinatorial immunotherapy offers a chance to dramatically
improve on this, at the cost of significant multi-system toxicity. This talk will discuss the issues involved in anticipating, detecting and managing immune-related side effects and outline possible mitigation strategies.
14:55 Novel Immune Monitoring and Biomarker Technologies to Support the Development of Combination Immunotherapies for the Treatment of Cancer.
Dirk Brockstedt, Ph.D., Senior Vice President, R&D, Aduro BioTech Inc.,
The approval of several immunotherapies including cancer vaccines and immune checkpoint inhibitors has not only transformed patient’s lives but also brought challenges to the conventional drug development paradigm and the use of typical
PK/PD markers to identify optimal patient populations as well as dose level and schedule. This talk will discuss novel immune monitoring and biomarker technologies that were applied for the development of Aduro’s Listeria-based cancer
immunotherapy for pancreatic cancer and mesothelioma.
15:25 Hormone-Immunotherapy in Endocrine-Dependent Metastatic Breast Cancer: Laboratory and Clinical Data
Andrea Nicolini, M.D., Clinical Researcher, Internal Medicine, University
of Pisa, Italy
Hormone therapy is currently advised for ER+ metastatic breast cancer patients however in most of them the arising of resistance is a not yet well understood hurdle to overcome. We hypothesized that in these patients during clinical benefit
from antiestrogen therapy the addition of cycles of sequential immunotherapy could prolong the benefit and delay the occurrence of acquired hormone resistance. In order to validate this hypothesis, in 1992 we started an open, prospective
exploratory clinical trial. Here we summarize and update the clinical data and focus on the main serum biomarkers that proved helpful to monitor the efficacy of hormone immune therapy
16:10 Extended Q&A with Session Speaker
16:25 Refreshment Break
16:45 CLOSING PANEL: Strategies for Practical Application of Biomarker Research
Dirk Brockstedt, Ph.D., Senior Vice President, R&D,
Aduro BioTech Inc., United States
Shao-An Xue, Ph.D., Genetic Engineering Laboratory, School of Biological &
Environmental Engineering, Xi’an University, Institute of Immunity & Transplantation, University College London Medical School, United Kingdom
Ekaterina S. Jordanova, Ph.D., Principle Investigator, Obstetrics and Gynaecology, Centre for Gynaecological Oncology Amsterdam, The Netherlands
Kenneth Emancipator M.D., Executive Medical Director, Translational Medicine,
Companion Diagnostics, Merck & Co., United States
- Sample quality, quantity, and type
- Standardizing procedures and assay validation
- Funding, resources, and collaboration
17:45 Close of Conference