Monday 18 March
9:30 – 12:30
SC1: The Tumour Microenvironment and Response to Cancer Immunotherapy
Stephen A. Beers, PhD, Professor of Immunology and Immunotherapy, Centre for Cancer Immunology, University of Southampton
Awen Gallimore, DPhil, Professor, Immunology, Infection and Immunity, Cardiff University
The tumour microenvironment (TME) is a complex, dynamic environment in which the behaviour of tumour cells alters in response to cues from the extracellular matrix (ECM), cytokines, immune cells, and stromal cells. As well as propagating tumour growth and spread, the TME may also influence the response to immunotherapy. For example, stromal cells such as fibroblasts may drive cancer growth through production of TGFβ whilst macrophages display immunosuppressive and tumour promoting properties, through driving tumour cell proliferation and survival. In this short-course we will discuss the nature of the TME and the multiple ways in which it promotes an immunosuppressive environment. Opportunities to alter the TME in order to more effectively deliver immunotherapy will also be discussed.
During the course we will discuss:
- The key components of the tumour microenvironment
- Immunosuppressive cells in the TME
- Immunosuppressive signalling pathways in the TME
- The influence of ECM proteins on tumour infiltrating T cells
- Overcoming immunosuppression in the TME
- The barriers to T cell entry and how these may be overcome
- Altering the TME to improve response to immunotherapies
- The importance of relevant model systems to assess drug candidates
SC2: Next Generation Immunotherapies
A short course featuring the exciting approaches being used by today’s immune-oncology scientists. You will learn about current successes and future potential, and how the leaders in the field overcome the challenges encountered.
1. Bispecific Antibodies: Formats, Considerations, Developability and Opportunities
Laura von Schanz, Director, Alligator Biosciences
Different bispecific formats will be examined as well as the challenges encountered with combining two antibody specificities in one molecule.
2. Immunocytokines: New Formats and New Strategies
Dario Neri, PhD, Professor, Biomacromolecules, Chemistry and Applied Biosciences, ETH Zürich
In this lecture, I will discuss various approaches which have been implemented in order to generate cytokine-based therapeutics with improved therapeutic index.
3. Cellular Therapies: Current Successes and New Directions
Ryan McCoy, Lead Technical Scientist, Cell and Gene Therapy, Catapult
This presentation will review current successes in the T-cell therapy space, whilst considering key industrial focal points for building an ecosystem to maximise their commercial realisation.
4. The Yin and the Yang of the Innate Immune System in Cancer Therapy
R.J. Tesi, MD, CEO and CMO, Inmune Bio
NK and macrophages are often inactive in patients with cancer, and MDSC and TAM that populate the TME protect the tumor from the immune system and immunotherapy. Effective therapeutic strategies must account for effector cell dysfunction and protector
cell function to be effective.
5. In vitro/ex vivo Models and Adapting in vivo Models to Study Immuno-Oncology and Antibody Functions
Sophia N. Karagiannis, BA, MS, PhD, Reader, Translational Cancer Immunology, St. John’s Institute of Dermatology, School of Basic & Medical Biosciences
We will discuss how one could utilize disease-relevant In vitro and ex vivo models to boost translational research.
THURSDAY 21 MARCH
18:30 - 21:30 (To Include Dinner)
SC3: Managing the Challenges of Bioassays for Immuno-Oncology
Sofie Pattijn, CTO, ImmunXperts
Gisèle Deblandre, CSO, MaSTherCell
During the last years, significant advancement has been made in the clinical application of cancer immunotherapies. Molecules directed against immune checkpoints and other agonists show great promise for treatment of a variety of malignancies. Early evaluation of the effectiveness of candidate therapeutics and combination therapies can be done using mouse models and in vitro bioassays with primary mouse or human immune cells.
Part One: Bioassays for Non-Cellular Products
This short course will present experiences and data regarding bioassays for immune-modulatory antibodies and combination approaches. It will address the challenges with:
- Dealing with the primary cells
- Importance of understanding the question you want answered and designing and interpreting an appropriate assay
- Translating the results
- Managing expectations
- It will examine:
- Prediction versus documenting MOA
- What the bioassay does, what it is measuring, what it means and its value.
- Technical challenges will be addressed
- Case studies with data
- It will examine:
Part Two: Bioassays for Cellular Products
This second part of the short course will focus on bioassays used to support clinical development of cell-based immunotherapies more specifically CAR or TCR T-cell therapies. It will address the challenges linked with the choice/design of assays for toxicity and potency assessment.
- Safety assays
- Risk assessment
- Assessment of off-target effects
- Assessment of tumorogenicity
- Predictivity of tumorogenicity assays
- Animal models for safety and toxicity
- Efficacy and potency assays
- Recapitulating a MOA in animal and in vitro models
- In vitro assays for potency
- Technical challenges
- Case study
SC4: T Cell Therapies: Current Field, Challenges and Future Directions
Fiona Thistlethwaite, Consultant, Medical Oncology, Experimental Cancer Medicine, and Honorary Senior Lecturer, Cancer Sciences, Biology Medicine & Health, University of Manchester
Reno Debets, PhD, Associate Professor, Tumor Immunology, Medical Oncology, Erasmus MC Cancer Institute
The field of Adoptive T cell (ACT) therapy is advancing rapidly and the EMA approval of products expressing CD19-specific Chimeric Antigen Receptor (CAR) to treat B cell malignancies marks the start of a new era. However, significant challenges remain and need to be addressed if momentum is to be maintained and these exciting new products are to become embedded within clinical practice. Challenges include the safety assessment of target antigen and corresponding CARs or T cell receptors (TCRs), optimisation of T cell fitness, and the search for combinatorial approaches to enable T cells to target solid tumors. In addition to the preclinical trajectory, it is important to roll out these therapies in the clinical setting, which includes steps such as the manufacture and testing of clinical grade vector, development of efficient and reliable manufacturing methods, and delivering the therapies to patients safely, effectively and at a cost that is considered reasonable. This workshop will explore these important issues as we look to transition ACT from the laboratory into mainstream medicine.
Points that are considered
- Selecting safe antigens and receptors for ACT
- Strategies to enhance therapeutic efficacy; and clinical trial design to incorporate combining ACT with standard treatments or other immunotherapies such as checkpoint inhibitors and vaccines
- Establishing best practice for delivery of ACT in a hospital setting; including monitoring and managing toxicities from ACT
- Challenges of scale-up as we move beyond single site investigator led-clinical trials
- Establishing links between the pharmaceutical industry and clinical centres to deliver ACT
- Humanized mouse models: In-house generation or outsourcing?
*Separate registration required