Cambridge Healthtech Institute’s 2nd Annual
Preclinical and Translational Immuno-Oncology
( 癌症免疫疗法的临床前研究与转译医学研究 )
Advanced Immuno-Oncology Models and How They Translate to the Clinic
Modeling the immune system and its response to cancer sets a particularly difficult challenge. The different cell types required, heterogeneity of tumours and the signaling pathways involved mean that multiple advanced models are required to justify clinical trials. But which ones do you choose and how do they relate to the clinic? At the Preclinical and Translational Immuno-Oncology conference, we will delve deeper into the advantages and disadvantages of each model and the strategies employed to help translate positive results to clinical trials. Models to be discussed include humanized mice models, syngeneic and xenograph models, 3D models and organoids, plus many more.
Day 1 | Day 2
Recommended Short Course*
SC1: Oncolytic Virus Therapy – Current Field, Challenges and Future Directions - LEARN MORE
Ulrich M. Lauer, MD, Professor, Vice Chairman, Internal Medicine VIII, Medicine, University Hospital Tübingen
Alan Melcher, MD, PhD, Professor, Team Leader, Translational Immunology, The Institute of Cancer Research
*Separate registration required.
7:30 Registration and Morning Coffee
8:30 Organizer’s Welcome Remarks
Joel Hornby, BSc Hons, Conference Director, Cambridge Healthtech Institute
8:35 Chairperson’s Remarks
Roger Sutmuller, PhD, Director of External Innovation, Oncology pRED, Roche Pharma, Roche Innovation Center Zürich
8:40 Partnering for Success: External Innovation as Essential Component for a Successful Cancer Immunotherapy Portfolio
Roger Sutmuller, PhD, Director of External Innovation, Oncology pRED, Roche Pharma, Roche Innovation Center Zürich
Cancer immunotherapy is a promising field in oncology. However, competition is fierce with currently hundreds of compounds in development. Diversity of thought, understanding biology and access to novel modalities is essential to progress cancer research. By joining forces between academia, biotech and pharma we can truly make a difference for cancer patients. This talk will cover our approach to leverage external innovation including case studies of recent collaborations.
9:10 Multidisciplinary Approaches to Enhancing Cancer Biotherapeutics within the CRUK City of London Centre
Tony Ng, FMEDSCI, MB, ChB, MRCP, FRCPath, PhD, Head of School of Cancer and Pharmaceutical Sciences, King’s College London; CRUK City of London Centre Executive Member; Richard Dimbleby Chair of Cancer Research; Group Leader, KCL Breast Cancer Now Research Unit; Director, KCL and UCL Comprehensive Cancer Imaging Centre; Chair of Molecular Oncology, UCL Cancer Institute
Within the cross-disciplinary approaches enhancing biotherapeutics theme of the CRUK City of London Centre, we use our cross-disciplinary strengths (engineering, physics, chemistry, mathematics) to maximise the impact of biological therapies. We are exploring responses to biological therapies in a manner analogous to pharmacokinetic/pharmacodynamic studies of small molecule-based therapies, using advanced imaging to track (pharmacokinetics) and quantify the impact (pharmacodynamics) of biological therapies thereby increasing our understanding of the immune-tumour interaction and effect on tumour microenvironment.
Erika Fletcher, PhD, Head of R&D, Immuneed
When a drug is administered into the human circulation, it can react with different components of the blood in both anticipated and unexpected ways. Immuneed’s platform, uses fresh, circulating blood with intact cascade systems. As a result, we address the specific challenges of each pharmaceutical, from nanoparticles to large biologics.
Jon Waterman-Smith, Director, European Business Development, Canopy Biosciences
Canopy’s next generation cytometry system provide actionable metrics for preclinical and clinical studies by detecting and quantitating functional immune subsets with single cell precision, whether in bloods or tissues, as well as analysing their spatial arrangement and relationship in tissues.
10:10 Coffee Break in the Exhibit Hall with Poster Viewing
10:50 Combinatorial Approaches to Enhance Bispecific Anti-Tumor Efficacy
Eric Smith, PhD, Senior Director, Bispecific Antibodies, Regeneron Pharmaceuticals
This presentation will describe Regeneron’s bispecific platform and present preclinical data on REGN4018, a clinical stage T cell engaging bispecific targeting Muc16 for solid tumor indications. In addition, status updates on Regeneron’s other clinical stage bispecific antibodies (REGN1979, REGN5458, REGN5678) will be presented as well as a discussion of new combinatorial approaches being taken to enhance bispecific anti-tumor efficacy.
11:20 Regulatory Strategies for Early Clinical Development
Elena Spanjaard, PhD, Global Head of Regulatory Affairs, Celyad
Regulatory guidelines provide a framework for preclinical development, and key regulatory concepts will be highlighted. Preclinical studies must be tailored to support individual product and development program features. Considerations for different immuno-oncology modalities will be presented, including a discussion on challenges and suggested approaches for successful development.
11:50 Translational Aspects of Tissue/Site Agnostic Indications
Andrew Exley, PhD, Medical Assessor, Biologicals and Biotechnology Unit, MHRA
Tissue or Site agnostic therapies in oncology are the epitome of precision therapies targeted to molecularly defined tumors. The first tissue agnostic approvals granted by the FDA in 2017, pembrolizumab for unresectable or metastatic, MSI-H or dMMR solid tumors and the orphan-drug designated larotrectinib and entrectinib for solid tumours with NTRK-fusion proteins, provide useful exemplars. We review the specific opportunities and challenges of this molecular approach.
Kader Thiam, PhD, Vice President, Transgenic Technologies, genOway
12:50 Dessert and Coffee Break in the Exhibit Hall with Poster Viewing
ADDRESSING NOVEL IO TARGETS
13:20 Chairperson’s Remarks
Jane Willoughby, Senior Post-Doc, Antibody and Vaccine Group, Centre for Cancer Immunology, University of Southampton
13:25 Tissue Distribution, Elimination and Target Engagement of Biologics – Going from Mice to Men and from in vivo to in Silico
Armin Sepp, PhD, Scientific Leader and GSK Fellow, IVIVT DMPK Modelling, GlaxoSmithKline
We describe a two-pore physiologically-based pharmacokinetic model to describe and predict the tissue distribution, elimination and turnover of soluble proteins, dosed or endogenous, from mice to men. The model includes all major organs and neonatal Fc receptor mediated recycling in the endosomal compartments. We evaluate the model by comparing the ab initio predictions for the tissue distribution and elimination properties of albumin-binding domain antibody with the experimental observations in humans.
13:55 DNA-Based Nanobody Delivery
Pieter Deschaght, PhD, Project Leader, Nanobody Explorative Technologies, Discovery, Ablynx - Sanofi
Small Nanobodies® with their modular design show a different pharmacokinetic profile compared to conventional antibodies and this can be exploited by alternative delivery methods. DNA-based gene transfer of Nanobodies and biopharmaceuticals in general is an appealing alternative to conventional protein therapy. We demonstrate that multivalent Nanobodies encoded as DNA results in a stronger, longer-term and more localized exposure compared to conventional protein therapy.
14:25 FEATURED PRESENTATION: Stress Induced Post-Translational Modifications (siPTMs) as Targets for Cancer Vaccines
Lindy Durrant, PhD, Professor of Cancer Immunotherapy, University of Nottingham; CSO, Scancell Ltd.
Citrullination is a widely expressed, novel, stress induced post-translational modification that is a potent target for cancer vaccines. There is a repertoire of cytotoxic CD4 T cells in mice and humans that recognises citrullinated epitopes. Tumors over-express PAD enzymes. Inflammation and stress induce high levels of autophagy and MHC-II presentation of citrullinated epitopes on tumors. Citrullinated peptides demonstrate potent anti-tumor immunity with no associated toxicity and will shortly enter the clinic.
Qingcong Lin, PhD, CEO, Biocytogen Boston Corp.
Biocytogen is a preclinical-stage, one-stop antibody drug development service provider covering innovative humanized mouse, in vivo and in vitro pharmacology studies, and therapeutic antibody discovery services. Recently, Biocytogen has developed a proprietary fully human antibody mouse (RenMabTM), which carries the complete repertoire of human antibody genes. The combination of RenMabTM mouse and gene-targeting technology greatly empowers novel therapeutic antibody generation against antibody targets, including challenging immuno-oncology and autoimmune disease targets.
15:25 Refreshment Break in the Exhibit Hall with Poster Viewing
16:05 TNFR2 Antagonism: Specificity for the TME and the TNFR2 Oncogenes
Denise Faustman, MD, PhD, Director of Immunobiology, Medicine, Harvard Medical School/Massachusetts General Hospital
Over the past 2 years, disappointing data has appeared on agonistic approaches to cancer with antibodies. The TNFR2 receptor is overexpressed in Tregs and MDSC and cancer cells thus antagonistic antibodies are desired. We now will show the novel pathway and binding specificity of this new class of antibodies.
16:35 Immunotherapy by Design – Induction of Systemic Anti-Tumour Immunity by Targeting Recruitment of Natural Antibodies
Melanie Glossop, BSc, CChem, FRSC, Head of Chemistry, Avvinity Therapeutics
Centauri Therapeutics is designing highly disruptive treatments for life-threatening bacterial infections and cancer using the power of natural antibodies. The technology has the potential to induce broad and universal anti-tumour immunity using proprietary Alphamers. Alphamers selectively bind their target and simultaneously recruit natural antibodies for engagement of both the innate and adaptive immune system.
17:05 Problem Solving Breakout Discussions (See complete list of Problem-Solving Breakout Discussion)
In Silico Modelling in IO, How Useful and Predictive?
Moderator: Armin Sepp, PhD, Scientific Leader and GSK Fellow, IVIVT DMPK Modelling, GlaxoSmithKline
- Target engagement in combination and bispecific therapies, when can one or the other be preferred?
- Tumour penetration of biotherapeutics
- Drug interactions with innate and adaptive immune system cells
How Can We Leverage Cutting Edge In Vivo Pre-Clinical Models for Cancer Immunotherapy Profiling?
Moderator: Mario Perro, PhD, Principal Scientist, Cancer Immunotherapy Pharmacology Department, pRED, Roche
- Current limitations of pre-clinical mouse models for cancer immuno-therapy
- How can CPI resistant patient population can be modeled pre-clinically
- New frontiers of tumor immuno-profiling
19:05 Close of Day
Day 1 | Day 2
7:45 Registration and Morning Coffee
ADVANCED IO MODELS
8:30 Chairperson’s Remarks
Sarvesh Kumar, PhD, MBA, Director, Laboratory Animal Sciences Program, Waldmann Lab Lymphoid Malignancies Branch, NCI/NIH
8:35 In vitro/ex vivo 3D Models to Address the Immune Tumor Microenvironment
Catarina Brito, PhD, Lab Head, Advanced Cell Models Lab, Animal Cell Technology Unit, iBET
We have been developing in vitro and ex vivo 3D cell models to depict features of the tumor microenvironment, such as the crosstalk between different cell players and the ECM remodeling, drivers of the immunosuppressive and invasive microenvironment typical of advanced stage carcinomas. Case studies in ovarian and breast cancer will be discussed, including the interrogation of chemotherapeutics and targeted drugs, including immunomodulatory ones.
9:05 How Can Cutting-Edge Preclinical Models Help Rational Cancer Immuno-Therapy Design?
Mario Perro, PhD, Principal Scientist, Cancer Immunotherapy Pharmacology Department, pRED, Roche
Preclinical mouse models are key tools to evaluate the activity of cancer immuno-therapy. Here we will present our cutting edge mouse models platform which allows the identification of relevant pharmacodynamic biomarkers, and helps design rational immunotherapy combinations. The translational relevance of the preclinical data obtained will be shown.
9:35 Ex vivo Profiling of PD-1 Blockade Using Organotypic Tumor Spheroids
Russell W. Jenkins, MD, PhD, Assistant Professor, MGH Cancer Center, Massachusetts General Hospital, Harvard Medical School
Ex vivo systems that incorporate features of the tumor microenvironment and model the dynamic response to PD-1 blockade may facilitate efforts in precision immuno-oncology. We have developed a system for ex vivo profiling of PD-1 blockade using 3D microfluidic culture of murine- and patient-derived organotypic tumor spheroids (MDOTS/PDOTS) using established murine models as well as clinically relevant patient specimens.
Holger Weber, PhD, Head of In Vivo Pharmacology, ProQinase
Introducing the next generation of tumor models for immuno-oncology efficacy studies overcoming common problems experienced with subcutaneous tumor implantation.
10:20 Sponsored Presentation (Opportunity Available)
10:35 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 Solutions-Focused Speed Networking in the Exhibit Hall
PLENARY KEYNOTE SESSION
11:15 Organizer’s Remarks
Ngoc ‘Emily’ Le, PhD, Conference Producer, Cambridge Healthtech Institute
11:20 Chairperson’s Remarks
Andrew Sewell, PhD, Distinguished Research Professor and Wellcome Trust Senior Investigator, Infection & Immunity, Cardiff University School of Medicine
11:30 Strategies to Improve Antitumor Efficacy of Genetically Engineered T Cells
Stanley Riddell, MD, Scientific Director, Clinical Research, Fred Hutchinson Cancer Research Center; Professor, University of Washington School of Medicine
Immune cells can be readily genetically modified to express natural tumor targeting antigen receptors or synthetic chimeric antigen receptors (CARs) that activate immune cell signaling pathways to result in destruction of tumor cells expressing the relevant target molecule. The presentation will discuss advances in our understanding of receptor signaling and the development of strategies that combine therapeutic agents to improve efficacy and safely extend the spectrum of cancers that can be treated with cell therapies.
12:00 PD-1 Antibodies Are Transforming Cancer Treatment
Roy D. Baynes, MD, PhD, Senior Vice President and Head, Global Clinical Development, CMO, Merck Sharpe & Dohme
PD-1 antibodies have shown significant activity as monotherapy across multiple cancer types and lines of therapy. Precision medicine tools have been used to identify subjects most likely to respond to PD-1 antibody monotherapy, to provide insight to potential resistance mechanisms, and to inform combination therapies. A number of these combinations have demonstrated significant activity in additional tumor types and lines of therapy.
12:30 Close of Preclinical and Translational Immuno-Oncology