Tuesday, 20 March, 18:30 – 21:30
Fiona Thistlethwaite, MB, PhD, Consultant, Medical Oncology, The Christie NHS Foundation Trust, 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 with the FDA approval of a T cell product expressing CD19-specific Chimeric Antigen Receptor (CAR) to treat B cell leukemias (tisagenlecleucel), it has entered a new era. However, significant challenges remain, including 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 the clinical setting, challenges include 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.
- Selecting safe antigens and receptors for ACT
- Strategies to enhance therapeutic efficacy
- 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
Thursday, 22 March, 18:30 – 21:30
Linda Martensson, Senior Research Scientist, Preclinical Research, Bioinvent
Valeria Nicolini, PhD, Principal Scientist, Pharmacology, Roche Innovation Centre
Part One: Preclinical Mouse Models in the Development and Selection of Therapeutic Immuno-Modulating Antibodies
This session will examine the pros and cons of the different types of animal model, the challenge of finding an antibody that cross reacts with mouse targets, and the need for surrogate antibodies or a humanized mouse model.
This session will examine different types of animal models for
A. Proof of Concept of new targets.
B. Choosing the optimal lead candidate.
- Surrogate antibodies in immunocompetent models
- Transgenic models expressing human targets
- Fcγ-receptor humanized models
- Patient-derived xenograft models
Part Two: Humanized Mouse Models: Technology and Applications in Preclinical Assessment of Cancer Immunotherapy
The course will describe different types of humanized mouse models, their immune characterization, and specific examples of their application in the field of cancer immunotherapy. The course will highlight advantages and pitfalls of currently available humanized mouse models and review next generation improved humanized models designed to better address specific immunological questions.
- Selection of humanized mouse model for specific immunotherapeutic applications
- Immunopharmacodynamic analyses in humanized mice: Impact of immunotherapeutic treatments on the immune cell contexture
- Humanized mouse models: In-house generation or outsourcing?
Mark Cragg, PhD, Professor, Experimental Cancer Biology, Antibody & Vaccine Group, Cancer Sciences Unit, University of Southampton
Ann White, PhD, Senior Principal Scientist, New Medicines, UCB
The tumour microenvironment (TME) is a complex, dynamic environment in which extracellular matrix (ECM), soluble factors, immune cells, stromal cells and tumour cells interact. Each of these components is key to the establishment and growth of the tumour, as well as impacting tumour cell behaviour and response to treatment. In this short course, we will discuss the nature of the TME, how the tumour promotes an immunosuppressive environment, and what opportunities this presents for reversing immune suppression to deliver effective immunotherapy.
During the course, we will discuss:
- The constituents of the tumour microenvironment
- Factors in the TME that may influence therapeutic response
- Immune cell frequencies and phenotypes
- Cross-talk between tumour and stromal cells – suppressive cytokines, influence on characteristics of tumour cells and ability to metastasise
- Extracellular matrix components
- Vascularity, barriers to T-cell entry
- Opportunities to overcome some of these factors
- A conceptual framework for how immunomodulatory mAb might best function
- How therapeutic success is likely to require combination approaches
- The importance of relevant model systems
*Separate Registration Required