2016 Archived Content
Cambridge Healthtech Institute’s Inaugural
Novel Immunotherapy Strategies
Exciting Developments with Promise in the Clinic
31 October - 1 November 2016 | EPIC SANA Lisboa Hotel | Lisboa PORTUGAL
Investigators who have believed in the potential of immunotherapy for years are finally being rewarded. Progress is being made with many different approaches, and evidence that they work is being seen in the clinic. We live in exciting times.
This conference track will include case studies on checkpoint inhibitors, CAR-T cells and other approaches, and will focus on the challenges encountered and, in many cases, overcome. Of particular interest is the product engineering, and the mode of action
together with the background immunology. Particular challenges with immunotherapy are to do with safety, GMP manufacture and with regulatory approval.
Final Agenda
Day 1 | Day 2 | Speaker Biographies | Download Brochure
MONDAY 31 OCTOBER
12:00 Registration
13:40 Welcome from PEGS Europe Team
13:45 Chairperson’s Opening Remarks
Ana Barbas, Ph.D., Coordinator, Bayer Satelite Laboratory at iBET, iBET and Bayer Portugal SA
13:50 Biotherapeutic Programs that Re-Direct Cytotoxic Lymphocytes to Cancer Cells
Paul Adam, Ph.D., Executive Director, Immune Modulation and Biotherapeutics Discovery, Boehringer Ingelheim
Cytotoxic lymphocytes such as NK and T cells have the capability to control cancer development and progression. Harnessing this cytotoxic potential with biotherapeutic agents is predicted to become a future pillar of cancer therapy in light of recent
clinical successes. This presentation will describe novel biotherapeutics whose mode of action involves the engagement and re-direction of NK and T cells to hematological tumors.
14:30 Antibody-Based Combination Cancer Immunotherapy at Roche pRED
Christian Klein, Ph.D., Distinguished Scientist, Head, Oncology Programs, Cancer Immunotherapy Discovery,
Roche Pharmaceutical Research and Early Development, Roche Innovation Center Zurich
This presentation will introduce novel antibody cancer immunotherapies developed at Roche pRED including novel IL2 variant immunocytokines and T cell bispecifics as well as preclinical data for their optimal combination and scheduling.
15:10 Safety Concerns Associated with Immunotherapy and Novel Biotherapeutics and Challenges in Investigating Their Immunotoxicity
Sandra S. Diebold, Ph.D., Principal Scientist, Immunotoxicology, Biotherapeutics, National Institute for
Biological Standards and Control (NIBSC)
The pre-clinical assessment of the risks associated with immunotherapy and novel biotherapeutics is challenging since the bioassays have to be individually tailored to the investigated reagent. The immunotoxic activity and adverse responses that may
be observed in patients are depending to a large degree on the mechanism of action of the biotherapeutic. The specific set-up of in vitro assays plus the identification of suitable animal models is critical for obtaining predictive pre-clinical
data.
15:50 Refreshment Break in the Exhibit Hall with Poster Viewing
16:50 Chairperson’s Remarks
Marie Kosco-Vilbois, Ph.D., CSO, Novimmune SA
16:55 Immunotherapy “From the Inside”
Stefan Dübel, Ph.D., Managing Director, Biochemistry, Biotechnology and Bioinformatics, Technische Universität
Braunschweig
We present approaches for inhibition of cell surface receptors or signalling pathways by novel strategies “from the inside”. We will inspire the biologics engineering community to start thinking out of the box by opening doors to targets
which so far could not be reached inside the cell, and to add extra punch or extra safety to biologics by targeting a combination of two disease specific features.
17:25 Clinical Development of Adoptive T-Cell Therapy in Melanoma and Beyond
Rienk Offringa, Ph.D., Head, Molecular Oncology of Gastrointestinal Tumours, German Cancer Research Centre
Adoptive transfer of tumour-infiltrating T cells has shown striking efficacy in patients with metastatic melanoma, even in late stage patients. T cells targeting neo-epitopes encoded by the tumour mutanome play a dominant role in this respect. Based
on this insight, adoptive T-cell therapy can now be further optimised and developed for the treatment of other cancer indications.
17:55 Quantitative Cell-Based Bioassays for Analysis of mAb Fc Effector and Immune Checkpoint Functions
Gopal Krishnan, Ph.D., Global Product Manager, Cellular Analysis & Proteomics, Promega
Immunotherapy is a promising therapeutic strategy to better fight cancer. We have developed many reporter bioassays for immune checkpoint, co-stimulatory and immunomodulatory receptors including combination bioassays (e.g., PD-1+TIGIT). The assays
can quantitatively determine the potencies of candidate antibody drugs or ligand proteins and are valuable tools for antibody screening.
18:10 Sponsored Presentation (Opportunity Available)
18:25 Welcome Reception in the Exhibit Hall with Poster Viewing
19:25 End of Day
Day 1 | Day 2 | Speaker Biographies | Download Brochure
TUESDAY 1 NOVEMBER
07:45 Registration and Morning Coffee
08:30 Chairperson’s Remarks
Saar Gill, M.D., Ph.D., Assistant Professor, Medicine, Hematology- Oncology, University of Pennsylvania School
of Medicine
08:40 Targeting Immune Regulation at the Tumour Site: Mechanistic Insights on Immune Modulatory Antibodies
Frederick Arce Vargas, Ph.D., Haematology, University College London Cancer Institute
By studying the mechanism of action of anti-CLTA-4 therapy in murine models, we have learned that the effectiveness of immune modulatory antibodies depends on the antibody isotype and not only on blocking or activating the signalling through their
targets. Furthermore, a systematic characterisation of the immunological landscape of human cancers has provided more insight on how to translate findings in murine models into clinical application in a rational way.
09:10 Targeted Protein Therapeutics – Alone and in Combination with Immunotherapy
Gregory P. Adams, Ph.D., Chief Development Officer, Viventia Bio
TPTs mediate direct tumour killing and offer the ability to activate anti-tumour immunity. In early phase clinical studies, intra-tumoural injection of Proxinium mediated impressive effects directly on injected tumours and indirectly on uninjected
tumours, suggesting the generation of an anti-tumour immune response. Clinical trial results and preclinical studies will be presented both examining the mechanisms underlying the indirect anti-tumour effect and evaluating the potential of combining
Proxinium with checkpoint inhibitors.
09:40 Problem-Solving Breakout Discussions
Table 1: Challenges with Targeting Immune Checkpoint Inhibitors
Moderator: Frederick Arce Vargas, Ph.D., Haematology, University College London Cancer Institute
Different ways in which the immune response is “checked” in cancer
- Screening antibodies to the desired target
- Finding appropriate mouse models for proof-of-concept
- Challenges encountered and overcome with CMC, especially purification
- Demonstration of safety
- Potential of combinations of co-stimulatory molecules and check-point blockers
Table 2: Challenges of CAR T-Cell Immunotherapies
Moderator: Saar Gill, MD, Ph.D., Assistant Professor of Medicine, Hematology- Oncology, University of Pennsylvania School of Medicine
- Different CAR T-cell approaches and their limitations
- Target selection, screening and validation for targeted delivery
- Means of overcoming the need for a customized approach
- Platform development, and product optimization
- Biomarkers for safety and efficacy
Table 3: Measure to Ensure your Immunotherapy Product is Safe from Cytokine Storms
Moderator: Sandra S. Diebold, Ph.D., Principal Scientist, Immunotoxicology, Biotherapeutics, National Institute for Biological Standards and Control (NIBSC)
- What causes cytokine storms?
- Challenges of developing reliable cytokine release assays
- How real is the danger of autoimmunity and off-target toxicity?
- What are the best models: humanized mouse; in vitro assays?
- MABEL Approaches
- Risk mitigation strategies
10:40 Coffee Break in the Exhibit Hall with Poster Viewing
11:20 Therapeutic Targeting of B7-H3 in Solid Tumours through Immune Enhanced Abs and DART Molecules
Paul Moore, Ph.D., Vice President, Cell Biology and Immunology, MacroGenics, Inc.
Complementary strategies targeting B7-H3, a B7-family member expressed on solid tumours, are undergoing clinical development. Enoblituzumab, an Fc-enhanced humanized anti-B7H3 mAb, exhibits favorable safety with preliminary evidence of activity and
T-cell modulation, supporting further development as monotherapy and combination with checkpoint inhibitors. To leverage the tumor lytic activity of T cells and drive their expansion, we have also developed MGD009, an Fc-bearing B7-H3xCD3 DART
molecule, currently in Phase 1 testing.
11:50 FEATURED PRESENTATION: CAR T Cell Immunotherapy Approaches in the Clinic
Renier J. Brentjens, M.D., Ph.D., Director, Cellular Therapeutics, Memorial Sloan-Kettering Cancer
Center
While chimeric antigen receptor (CAR) approaches have resulted in significant clinical benefit with some CD19-B cell malignancies, far more modest outcomes are seen in patients treated with chronic lymphocytic leukemia (CLL). I will present next
generation CAR T cell approaches that directly target and kill tumour cells, modulate and overcome the immunosuppressive tumour microenvironment and recruit endogenous anti-tumour immune effector cells to avoid tumour immune escape.
12:20
Cancer Biotherapeutics - Affimers: A Novel Scaffold for Biotherapeutics
Amrik Basran, Ph.D., CSO, Therapeutics, Avacta Life Sciences
Affimers® are a new protein scaffold with great potential for the generation of biotherapeutics. Based on the protease inhibitor Stefin A, large diverse libraries have been created by engineering in peptide loops into the scaffold backbone.
Using phage display, we have identified competitive binders to a ranage of targets, including the immune check point, PD-L1. We have shown that the scaffold is amenable to being engineered with a range of half-life extension technologies.
12:50 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
13:20 Session Break
14:00 Dessert Break in the Exhibit Hall with Poster Viewing
14:30 Chairperson’s Remarks
Kerry Chester, Ph.D., Professor, University College London, Cancer Institute
14:35 Clinical Advances in CAR T Cell Therapy with a Focus on Anti-CD19 CARs
Saar Gill, M.D, Ph.D., Assistant Professor, Medicine, Hematology- Oncology, University
of Pennsylvania School of Medicine
Currently more than 70 clinical trials using CAR T cells, most of them targeting CD19, are open worldwide. Patients with B-cell malignancies are the first beneficiaries of an exciting and potent new treatment that harnesses the power of the
immune system as never before. These patients represent the vanguard of enormous preclinical efforts to develop CAR T therapy into a procedure that hopefully will one day be routine and curative.
15:05 Tumour Models to Investigate CAR T Cell Potency, and Acute and Chronic Toxicity
David Gilham, Ph.D., Vice President, R&D, Celyad S.A.
Reports of objective clinical responses and tumour regression in patients receiving Chimeric Antigen Receptor (CAR) -T cell therapy are driving a major surge of interest in the field. CARs are artificial targeting proteins that exploit antibody-based
approaches to re-direct the effector function of the T cell to virtually any cell surface target. However, it remains unclear whether toxicity resulting from over-activity of the T cell or lack of suitable target specificity is likely
to be an issue. Models can provide some answer to this although the relevance of such models remains open to question.
15:35 ErbB-Targeted CAR T cell Immunotherapy of Cancer
Daniela Achkova, Ph.D., Research Associate, Research Oncology, King’s College London
We have developed a CAR-based T4 immunotherapy approach targeting 8 of 9 possible ErbB homo- and heterodimers. Efficacy has been demonstrated in established xenograft models of head and neck, ovarian, breast cancer and mesothelioma in vivo.
Although this immunotherapy also recognises mouse ErbB receptors, toxicity does not occur following intra-tumoural administration. To exploit this, we have initiated a Phase I trial of T4 immunotherapy in patients with locally advanced/
recurrent squamous cell cancer of the head and neck.
16:05 Panel Discussion on Pros and Cons of the Different Approaches: CAR-Ts, Modified TCRs and TILs
Kerry Chester, Ph.D., Professor, UCL Cancer Institute
16:35 Refreshment Break in the Exhibit Hall with Poster Viewing
17:15 Taking SPEAR T Cells to the Clinic – From TCR Target Selection to Clinical Manufacture
Jo Brewer, Ph.D., Director, Cell Research, Adaptimmune
SPEAR (Specific Peptide Enhanced Affinity Receptor) T-cell therapy, using engineered T-cell receptors (TCRs), is showing clear promise in sarcoma and multiple myeloma trials targeting NY-ESO. Trials are now open with other TCRs: MAGE A10
& AFP – and there will be more to come. I will discuss the lifecycle of a SPEAR T-cell product from target selection, TCR identification and optimization, preclinical safety testing and manufacturing to make a robust, clinical
product suitable for commercial use.
17:45 B Cells and Antibody Responses in Solid Tumours
Sophia N. Karagiannis, Ph.D., Senior Lecturer, Translational Cancer Immunology,
Head, Cancer Antibody Discovery and Immunotherapy, St. John’s Institute of Dermatology, Division of Genetics and Molecular Medicine, King’s College London
The nature and contribution of circulating and tumour-infiltrating B cells and the antibodies they produce remain largely unexplored. We report active B-cell immune surveillance and mature memory B cells with distinct immunoglobulin
isotype-biased profiles in melanoma. We provide evidence in support of monitoring the humoral immune compartment in cancer to provide new prognostic tools and to inform therapeutic antibody design.
18:15 Bi- and Tri-Functional Antibody-Cytokine Fusion Proteins for Cancer Immunotherapy
Dafne Mueller, Ph.D., Group Leader, Cell Biology and Immunology, University of Stuttgart
IL-15 and costimulatory members of the B7 and TNF superfamily have shown great potential to support the generation and development of an anti-tumour immune response. In order to improve the efficacy of such molecules at the tumour site
we designed bi- and tri-functional antibody-fusion proteins, focusing on targeted presentation and combined mode of action of diverse immunomodulatory molecules, demonstrating enhanced immune responsiveness in vitro and anti-tumour
activity in a mouse model in vivo.
18:45 End of Novel Immunotherapy Strategies
Day 1 | Day 2 | Speaker Biographies | Download Brochure