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Immuno-Oncology: How to get the immune system to beat cancer

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Overview

This Royal Society meeting will explore immuno-oncology therapies - both current and recent technologies - whilst looking at removing barriers to their use. 

Credit: Design Cells

Background

Every two minutes, someone in the UK is diagnosed with cancer. Year on year, the cancer incidence rate continues to grow, with a projected increase of approximately 62% by 2040, resulting in over 27 million additional worldwide cancer cases per year. Traditionally, cancer has been treated using methods such as chemotherapy and radiotherapy. However, some cancers don’t respond well to traditional therapies, and others recur.  

Immuno-oncology could help provide a solution to these problems by harnessing the body’s immune system to eradicate cancer and prevent its recurrence. Through combination therapy, and addressing the barriers to its use, immuno-oncology treatments could help tackle the rising number of worldwide cancer cases. 

About the conference series

The conference is part of the Royal Society's Transforming our future conferences in the life sciences, supported by AstraZeneca. These  meetings are unique, high-level events that address the scientific and technical challenges of the next decade. Each conference features cutting edge science from industry and academia and brings together leading experts from the scientific community, including regulatory, charity and funding bodies.

Event organisers

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Schedule of talks

24 March

13:00-13:05

Welcome Remarks

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13:00-13:05 Welcome Remarks

Professor Dame Linda Partridge FMedSci FRS, Director, Institute of Healthy Ageing, University College London

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13:05-14:05

Opening keynotes

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Chairs

Dr Susan Galbraith FMedSci, SVP Early Oncology, AstraZeneca

13:05-13:35 The Evolution of Immuno-oncology: An Industrial Perspective

Dr Klaus Urbahns, Global Head of Discovery & Development Technologies, Healthcare R&D, Merck KGaA

Abstract

With the advent of checkpoint inhibitors, immuno-oncology has experienced a remarkable renaissance, offering today an enlarged and relatively well tolerated spectrum of therapeutic options to patients. In particular, antagonists directed against the Programmed death-1 (PD-1) protein and its ligand are now widely used clinically, often in combination with appropriate biomarkers. However, whilst some patients exhibit full responses including remissions, some tumours don’t seem to respond satisfactorily or even not at all. The pharmaceutical industry is working intensely to identify combination partners of checkpoint-based backbone therapies as well as completely novel approaches in order to improve the robustness and durability of these treatments. The presentation will cover the key therapeutic modalities the industry is currently examining, highlighting their potential, limitations and recent successes. The importance of academic research as well as the dialogue between the industry and payors will also be highlighted.  

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13:35-14:05 Chromosomal instability and immune evasion in cancer evolution

Professor Charles Swanton FRS FMedSci, Translational Cancer Therapeutics Laboratory Group Leader, The Francis Crick Institute

Abstract

TRACERx is a longitudinal cancer evolution study that aims to understand the interaction of complex evolving heterogeneous tumours with the tumour microenvironment across hundreds of patients. We have found that Chromosomal instability, is a major driver of intratumour heterogeneity contributing to parallel evolution, subclone selection and poor clinical outcome. The diversity of such tumour subclonal events in late stage tumours combined with tumour plasticity will likely confound the ability of monotherapy drugs targeting single clonal driver events to achieve sustained clinical benefit. We have found that tumour clonal neoantigens that may be recognized by cytotoxic T cells are major determinants of clinical outcome in treatment naïve and immune checkpoint inhibitor therapy treated patients, providing a therapeutic vulnerability in cancers with a high mutational burden. However, TRACERx has revealed multiple tumour adaptive mechanisms to immune predation, highlighting cancer chromosomal instability driving immune evasion through HLA class I and clonal neo-antigen loss as major routes to immune escape. How cancer genetic diversity limits an effective immune response and the role of clonal neoantigens as therapeutic targets to mitigate resistance and treatment failure will be discussed.

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Session 1 14:20-15:35

Cell Therapy Approaches

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Chairs

Dr Susan Galbraith FMedSci, SVP Early Oncology, AstraZeneca

14:20-14:45 Programming cells through genetic engineering – Advancing cell therapy innovation

Jo Brewer, SVP Allogeneic Research, Adaptimmune Ltd.

Abstract

Autologous T-cell therapies are now on the market and many more innovative T-cell products are in pre-clinical or clinical trials to treat a wide range of cancer patients. The recent explosion in cell modification techniques, through viral vectors and specific genetic editing, coupled with the ever-expanding knowledge of the human genome, provides a powerful toolkit for drug developers to improve on current therapies. Arming cells with receptors to enable them to recognise tumours efficiently, as well as adapting them to traffic to tumours more effectively and overcome resistance mechanisms, can generate improved products. A key factor for these treatments is understanding the cells themselves. The move from individual patient manufacturing towards “off-the-shelf” allogeneic alternatives should enable deeper product understanding and greater consistency. When multiple patients can be treated with the same batch of cells, from healthy donors or differentiated stem cells, it is possible to iterate product design based on translational data without the confounding factor of variable starting material – which will be an important step forward in the constant search for higher response rates and ultimately cures.

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14:45-15:10 Manufacture and delivery of cell therapies

Dr Stanley Frankel, Associate Professor of Medicine, Columbia University Vagelos College of Physicians and Surgeons

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15:10-15:35 CAR-T cell therapy in the clinic: lessons learned and road ahead

Dr Attilio Bondanza, Head of Clinical Development, Cell Therapy Unit, Oncology R&D, AstraZeneca

Abstract

T cell genetically modified to express chimeric antigen receptor (CAR-T cells) are a radically innovative way for tackling cancer. CAR-T cells have demonstrated unprecedented curative potential in diseases such as pediatric acute lymphoblastic leukaemia, non-Hodgkin lymphoma and multiple myeloma. The talk will focus on the science behind CAR-T cells, the determinants driving therapeutic efficacy and on aspects related to manufacturing and supply. Moreover, recognized gaps for translating CAR-T successes to solid tumours will be discussed.

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Session 2 15:50-17:05

Recent Immuno-oncology Breakthroughs

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Chairs

Professor Luke O'Neill FRS, Chair of Biochemistry, Trinity College Dublin

15:50-16:15 The role of the gut and tumor microbiome in cancer

Dr Jennifer Wargo, Professor, Department of Genomic Medicine, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center

Abstract

We have made major progress in the treatment of cancer: however, responses to cancer treatment are heterogenous and not always durable. There is a growing appreciation of factors impacting carcinogensis and canner therapy response, with the microbiome taking center stage. Within our bodies, we have trillions of microbes that may outnumber our own normal cells – and these microbes and their genomes (collectively referred to as the microbiome) can profoundly impact our physiology. The microbiome and its relationship to cancer will be discussed, including the tumor and gut microbiome.

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16:15-16:40 Using genomics for the design and response monitoring of personalized cancer vaccines

Dr Elaine Mardis, co-Executive Director of the Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital

Abstract

In addition to its role in identifying cancer drivers that may be predictive of response to targeted therapies, genomic characterization of individual cancers provides a data set to identify potential neoantigens and predict their binding affinity for class I and class II MHC.  Our efforts to produce a computational pipeline and tool set for these purposes will be described along with current data obtained from their use to characterize GBM samples from an accruing clinical trial of DNA-based personalized neoantigen vaccines.  In addition, the use of genomics-based methods to evaluate immune responses post-infusion will be outlined.

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16:40-17:05 Oncolytic immuno-virotherapy: promises, technical barriers, and recent progresses

Dr Eric Quemeneur, Executive Vice President, and Chief Scientific Officer, Transgene

Abstract

The approval of talimogene laherparepvec, and the large number of clinical trials with encouraging intermediate results should not make us forget the major challenges to install oncolytic viruses (OVs) as a new recognized therapeutic class.

These clinical developments have highlighted the key features for potent OV candidates, and also some specific properties requested for some applications. The ability to deliver large recombinant payloads into the tumor, i.e. armed OVs, is one of them as it provides additional therapeutic levers such as local activation of effector cells, blockade of immunosuppressive pathways, or metabolic modifications. 

In parallel, current research aims at overcoming the major obstacles encountered by OVs in their mode of action. These barriers might both be biological and physical. We will share some lessons learned from the development of Vaccinia-based oncolytic products, and some recent progresses in virus bioengineering or in delivery techniques that have raised optimism. 

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25 March

Session 3 13:45-15:00

Barriers and Pitfalls

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Chairs

Professor Sir Roy Anderson FMedSci FRS, Professor of Infectious Disease Epidemiology, Imperial College London

13:45-14:10 Artificial intelligence for digital tissue biomarker discovery in immuno-oncology

Dr Günter Schmidt, Vice President, Image Data Science, AstraZeneca

Abstract

Artificial Intelligence (AI) systems have surpassed human intelligence, fueled by the availability of dedicated high performance hardware, sophisticated deep learning architectures and algorithms, and Big Data. Deep convolutional neural networks have been successfully used to generate quantitative insights into the cancer immune contexture, and to replicate pathologists diagnostic scoring of tissue slides. However, the discovery of predictive biomarkers for immuno-oncology using computational pathology remains challenging. Standard fully supervised deep learning methods require extensive training data from expert pathologists. Latest weakly supervised methods aim towards superhuman performance, but frequently lack interpretability and transparency. Although regulatory authorities such as the FDA are increasingly open to approve AI "software as a medical device" systems, no histopathology-based companion diagnostic test has been yet marketed. The recent CE marks for prostate and breast cancer detection by AI-based clinical grade systems are promising milestones towards a wider adoption of computational pathology in the clinical routine, for the benefit of our patients.

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14:10-14:35 Employing novel technologies to improve immunotherapy

Professor Emile Voest, Netherlands Cancer Institute, The Netherlands

Abstract

Immunotherapy has significantly improved the outlook of patients with cancer. Early studies have shown benefit of check point inhibitors in metastatic cancer and now neoadjuvant immunotherapy has shown the curative potential of this treatment. However, the majority of patients do not have benefit of this treatment and studies to better understand mechanisms of resistance or allow better patient selection are highly needed. We have employed preclinical models to better understand the interaction between cancer cells and the immune system. These models provide new insights and pave the way to individualized immunotherapy.

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14:35-15:00 Tumor Re-Engineering: Developing Novel Immuno-Gene Therapies for Cancer

Dr Brian Champion, Chief Scientific Officer, PsiOxus Therapeutics

Abstract

Combining different anti-cancer immunotherapeutics is currently a major focus of clinical oncology studies, but while this can increase efficacy this benefit usually comes at a price of increased, dose limiting toxicity.  Because these agents are dosed systemically, they frequently cause unwanted immune inflammation in a variety of organ systems as well as in the intended tumor lesions.

Tumor re-engineering aims to overcome these issues by enabling selective delivery to and/or production of the therapeutic agent or combinations in tumor tissues where they are needed while minimizing systemic exposure.  We are developing a tumor-specific immune-gene (T-SIGn) vector approach that delivers biotherapeutic gene payloads for production by the tumor cells themselves.  These aim to promote anti-tumor immunity from within the lesions by targeting elements of the tumor and local lymphoid microenvironments. This presentation will use data generated with different clinical and preclinical stage T-SIGn candidates to illustrate these concepts.  

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Session 4 15:20-16:20

Panel discussion: Solving the issues of cost and regulations for new therapeutics

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Dr Stuart Farrow, Director of Biology, Cancer Research UK Therapeutic Discovery Laboratory
Dr Jacqueline Barry, Chief Clinical Officer, Cell and Gene Therapy Catapult
Professor Fiona Thistlethwaite, Medical Oncology Consultant, The Christie NHS Foundation Trust

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16:30-17:00

Closing Keynote

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16:30-17:00 Cancer Immunotherapy: Today's Triumphs and Tomorrow's Treatments

Dr Laurie Glimcher, President and CEO, Dana-Farber Cancer Institute

Abstract

Cancer cells induce a set of adaptive response pathways to survive in the face of stressors due to inadequate nutrient supply. One such adaptive pathway is the unfolded protein (UPR) or endoplasmic reticulum (ER) stress response mediated in part by the ER-localized transmembrane sensor IRE1 and its substrate XBP1. XBP1 promotes intrinsic tumor growth directly in the setting of triple negative breast cancer and also regulates the host anti-tumor immune response. A hostile tumor microenvironment (TME) composed of adaptive and innate immune cells that secrete or express immunosuppressive substances is one of the major barriers to achieving T cell-mediated tumor lysis. Reprogramming these immune cells through silencing the ER stress response reprograms a hostile TME to initiate and sustain T cell-dependent anti-cancer immunity. Targeting the ER stress response should concomitantly inhibit tumor growth and enhance anti-cancer immunity, thus offering a unique approach to cancer immunotherapy. 

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Immuno-Oncology: How to get the immune system to beat cancer

This Royal Society conference will explore immuno-oncology therapies - both current and recent technologies - whilst looking at removing barriers to their use.

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