2016 Archived Content
Cambridge Healthtech Institute’s Inaugural
Novel Therapies for Cancer and Emerging Targets
Improving Efficacy for Clinical Success
3 - 4 November 2016 | EPIC SANA Lisboa Hotel | Lisboa PORTUGAL
The Novel Products for Cancer and Emerging Targets track will explore the burgeoning field of antibodies, multi-modal proteins, cytokines and fusion proteins against oncology targets. It will feature an investigation of emerging targets
for cancer, including intracellular targets, cancer stem cell and checkpoint inhibition. New and clever ways of engaging the immune system will be explored, along with new approaches on how to engineer the next generation of CAR-T cells to be more
effective. The field is exploding with opportunities to develop the next generation therapies against cancer that promise greater efficacy and less toxicity. At this meeting, a realistic view of the current challenges facing development will be offered.
Scientific Advisory Board
Neil Brewis, Ph.D., Chief Scientific Officer, F-star
Soldano Ferrone, M.D., Ph.D., Division of Surgical Oncology, Surgery, Massachusetts General Hospital, Harvard Medical School
Mitchell Ho, Ph.D.,
Chief, Antibody Therapy Section, Laboratory of Molecular Biology, National Cancer Institute, NIH
Horacio G. Nastri, Ph.D., Senior Director, Antibody Biotherapeutics, Incyte Corporation
Final Agenda
Day 1 | Day 2 | Speaker Biographies | Download Brochure
THURSDAY 3 NOVEMBER
12:30 Registration
13:00 Dessert Break in the Exhibit Hall with Poster Viewing
13:30 Chairperson’s Opening Remarks
Horacio G. Nastri, Ph.D., Senior Director, Antibody Biotherapeutics, Incyte Corporation
13:35 KEYNOTE PRESENTATION: Antibody Functional Diversity as the Key to Unlocking Novel Target Biology
Christophe Blanchetot, Ph.D., Director, Discovery, argenx
Argenx is engaging with academic centers of excellence to secure early access to exciting, novel targets where proof of
concept in disease models is yet to be shown. Through its so-called Innovative Access Program, argenx brings its proprietary antibody technologies and know-how to collaborations with target biology specialists, enabling rapid progress into
translational studies and creation of novel antibody candidates with therapeutic product potential.
14:20 Immune Checkpoint in Melanoma
Ester Simeone, Ph.D., Director, Medical Oncology, Istituto Nazionale Tumori Napoli
Over the last few years, through numerous clinical trials and real-world experience, we have accumulated a large amount of evidence regarding the potential for long-term survival with immunotherapy agents in various types of malignancy. The results
of these studies have also highlighted a number of recurring observations with immuno-oncology agents, including their potential for clinical application across a broad patient population and for both conventional and unconventional response patterns.
14:50 Preclinical Development of Tumor Penetrating Anti-Nucleolin Antibodies with Broad-Spectrum Anticancer Activity
Daniel Fernandes, Ph.D., Chief Scientific Officer, Research Division, CharlestonPharma
Our Company has identified and validated a high value therapeutic target in oncology and has developed first-in-class fully human monoclonal antibodies that bind specifically to this target. A key concept which drove the selection process was that
the tumor antigen should be present on the surface of a wide variety of cancer cells with negligible or no expression on the surface of the corresponding normal tissues. In addition, cell surface expression of the therapeutic target should be
necessary for the survival of most types of cancer cells.
15:20 Refreshment Break in the Exhibit Hall with Poster Viewing
16:05 Addressing the Challenges in Effective Cancer Vaccine Development
Pedro Romero, M.D., Professor, Associate Director, Fundamental Oncology, Ludwig Cancer Research Center, Faculty
of Biology and Medicine, University of Lausanne
The recent breakthrough with immune checkpoint inhibitors has shown that the adaptive immune system can eliminate a wide range of tumors in a subset of cancer patients. The absence of naturally acquired T-cell responses to cancer antigens may be one
of the reasons for failure of immune checkpoint blockade therapy, thus providing a strong incentive to accelerate vaccine development. Rapid optimization of cancer vaccines is urgently needed to attain significant clinical impact.
16:35 Anti-Glycan Monoclonal Antibodies for Cancer Therapy
Mireille Vankemmelbeke, Ph.D., Senior Research Fellow, Academic Unit of Clinical Oncology, University of Nottingham
Glycomic profiling of tumour tissues consistently shows alterations in N- and O-glycosylation profiles of glycoproteins and glycolipids compared to healthy tissues, with important functional implications for cancer cell biology. Despite the attractiveness
of the targets, there are very few mAbs recognising glycans as they typically induce low affinity IgM responses. In this talk, we will show how we have overcome this limitation using complex immunisation regimes.
17:05 End of Day
17:00 Dinner Short Course Registration
Day 1 | Day 2 | Speaker Biographies | Download Brochure
FRIDAY 4 NOVEMBER
08:00 Registration and Morning Coffee
08:30 Chairperson’s Remarks
Neil Brewis, Ph.D., CSO, F-star
08:35 Anti-Cytokine Bispecific Antibodies for Asthma: A Brief History of the Ups and Downs
Daniel Rycroft, Investigator, PTS, GlaxoSmithKline
Developing bispecific antibodies that are both manufacturable and clinically developable is challenging. This talk will describe some of the issues we have encountered and what we have learned, focusing on strategies to select the best molecules from
the outset, understanding molecule conformation under stress and how we can use this data to build confidence to progress to the clinic.
09:05 In vivo Efficacy of Bispecific Antibodies Targeting Two Immune-Modulatory Receptors
Jacqueline Doody, Ph.D., Vice President, Immunology, F-star Biotechnology Ltd.
Combining immunotherapeutic antibodies has shown benefits over single agent in treating cancer patients. Bispecific antibodies are an alternative that not only bring two biologies together but results in novel biological mechanisms. F-star has a unique
bispecific format that allows two antigen binding sites to reside within a normal IgG framework. Using this format, several immunomodulatory bispecifics were produced for proof of concept studies in murine tumour models.
09:35 IMCgp100: A Novel TCR-Based Immunotherapy against Malignant Melanoma
Joseph Dukes, Ph.D., Head, Pre-Clinical Biology, Cell Biology, Immunocore
ImmTACs are bi-specific reagents that target tumors via a soluble monoclonal TCR with exceptionally high sensitivity and specificity and redirect host polyclonal T-cells via an anti-CD3 antibody fragment. Emerging data from the first ImmTAC, IMCgp100,
to enter Phase I/IIa clinical trials demonstrate durable responses in patients with advanced melanoma and a favorable safety profile. Development of IMCgp100 continues in uveal and cutaneous melanoma and in combination with checkpoint inhibitors.
10:05 Coffee Break in the Foyer with Poster Viewing
10:30 Chairperson’s Remarks
Mitchell Ho, Ph.D., Chief, Antibody Therapy Section, Laboratory of Molecular Biology, National Cancer Institute, NIH
10:35 CAR Modified Autologous Cells – CMC of an ATIMP
Christoph Priesner, Qualified Person, Quality Manager, Institute of Cellular Therapeutics,
Hannover Medical School
Gene-therapy medicines are re-emerging as promising pharmaceutical candidates for especially haemato-oncological indications. The patient-specific manufacture of genetically modified and expanded cellular therapeutics as investigational medicinal
products challenges multi-purpose academic cell processing units as regards biosafety requirements and analytical expertise to regulatory requirements. Highlighting these aspects, we present a case study on the academic-industrial co-development
and academic manufacture of an advanced therapy investigational medicinal product.
11:05 CAR T cells: From the Mouse Cage to the Patient’s Health
Zelig Eshhar, Ph.D., Professor, Chemical & Cellular Immunology; Chair, Laboratory of Cancer Immunotherapy,
Immunology, Weizmann Institute of Science and Tel Aviv Sourasky Medical Center
Along with Eshhar’s interest in the molecular recognition in the immune system, his lab. pioneered and developed the “T-Body” unique immune cell approach that involves genetic modifications of T-cells that is called today CAR
T-cell, or as he nicknamed it “T body”, which is being used to fight cancer. The genetically-engineered T cells have been shown to effectively kill human tumor cells both in vitro, and in experimental modes to treat local as well
as metastatic disease. Lessons learnt from these pre-clinical trials have been applied end-stage patients with B cell lymphomas and leukemias resulting in a large proportion (>45%) of remission.
11:35 Glypican-3 as a Liver Cancer Target for Antibody-Based Therapies
Mitchell Ho, Ph.D., Senior Investigator and Chief, Antibody Therapy Section, Laboratory of Molecular Biology,
National Cancer Institute, NIH
My lab has pioneered the production of inhibitory antibodies that recognize tumor-specific heparan sulfate proteoglycans. These antibodies have been shown to inactivate the Wnt/Yap signaling pathway known to be important for cancer pathogenesis.
We have established glypican-3 as an immunotoxin target for the treatment of liver cancer. Its mechanism of action appears to involve both inhibition of cancer signaling (Wnt/Yap) and reduction in protein synthesis. Our ongoing development
of chimeric antigen receptors for T-cell immunotherapy will also be discussed.
12:05 A "Trojan Horse" Bispecific Antibody Strategy for Broad Protection Against Ebolaviruses
Elisabeth K. Nyakatura, Ph.D., Senior Research Fellow, Department of Biochemistry, Albert Einstein College of Medicine
Ebola virus (EBOV) and related filoviruses are associated with sporadic outbreaks of highly lethal hemorrhagic fever in sub-Saharan Africa. The recent EBOV outbreak in West Africa has underscored the urgent need for antiviral treatments and demonstrated
the potential of passive immunotherapy to reverse advanced filovirus disease. However, existing monoclonal antibody (mAb) cocktails such as ZMapp are limited by a narrow spectrum of antiviral action, which stems from viral strain-specific
neutralization of the highly variable entry glycoprotein, GP, by most mAbs. Ebolaviruses engage the intracellular late endosome residing receptor Niemann-Pick C1 (NPC1) during host cell entry and infection. This engagement is absolutely required
for host cell infection and the receptor-binding site (RBS) on the filovirus glycoprotein is shielded prior to physical sequestration in late endosomes. To target this interaction, we developed a "Trojan Horse" bispecifc antibody strategy,
in which the viable domains of NPC-1 or GP-RBS specific antibodies are fused to an antibody that binds to a conserved surface exposed GP-epitope, applying Dual Variable Domain immunoglobulins (DVD-Ig). These bispecific molecules, but not their
parental monoclonal antibodies, neutralized all known ebolaviruses by utilizing the viral particle themselves for endosomal delivery, and conferred post exposure protection against multiple filoviruses in vivo.
12:35 Problem-Solving Breakout Discussions with a Light Snack in the Foyer
Do We Really Need New Targets?
Moderator: Horacio G. Nastri, Ph.D., Senior Director, Antibody Biotherapeutics, Incyte Corporation
• Why do we need new targets?
• What is working and what is not?
• Do we need new strategies to identify new targets?
• How do we improve validation efficiency and speed?
Getting CAR T to Work on Solid Tumors
Co-Moderators: 
Soldano Ferrone, M.D., Ph.D., Division of Surgical Oncology, Surgery, Massachusetts General Hospital, Harvard Medical School
Mitchell Ho, Ph.D., Chief, Antibody Therapy Section, Laboratory of Molecular Biology, National Cancer Institute, NIH
•
How to select the right targets?
• How to enhance the anti-tumor activity?
• What are the suitable mouse models to evaluate CAR-T therapy?
• Do we need to target cancer initiating cells? Do we have to take
into account hypoxia in the tumor microenvironment?
13:35 Session Break
14:00 Chairperson’s Remarks
Soldano Ferrone, M.D., Ph.D., Division of Surgical Oncology, Surgery, Massachusetts General Hospital, Harvard Medical School
14:05 Why Do CAR T cells Not Work in Solid Tumors Yet?
Attilio Bondanza, M.D., Ph.D., Head, Innovative Immunotherapies Unit, San Raffaele University Hospital
and Scientific Institute
While CAR T-cells have demonstrated remarkable antitumor activity in hematological malignancies, they currently struggle to achieve significant results in solid tumors. Target-antigen choice, in vivo persistence and the penetration of CAR T-cells
in the hostile microenvironment of solid tumors are among the factors potentially limiting their efficacy in other cancer indications. This talk will focus on each of these factors and propose innovative approaches for successfully circumventing
them.
14:35 Why CAR T Cells can Work in Solid Tumors! Novel CAR Technologies and Tumor Models
Michael Hudecek, M.D., Max Eder Research Group Leader, ‘CAR T Cell Engineering’, Medicine II, Universitätsklinikum Würzburg
A current challenge is to establish CAR T-cell therapy in the context of solid tumors. We developed a CAR specific for the antigen ROR1 that is expressed on epithelial cancers and demonstrated the ability of ROR1-specific CAR T-cells to confer
anti-tumor reactivity in pre-clinical models. We are in the process of establishing GMP manufacturing in preparation for a clinical trial exploring the safety and efficacy of this therapeutic modality.
15:05 Defects in T Cell Trafficking Within Human Tumors
Emmanuel Donnadieu, Ph.D., Team Leader, Immunology, Inflammation and Infection, Cochin Institute, INSERM
Our projects aim to identify the different obstacles that block T cells in their anti-tumor activities. The role of the extracellular matrix and tumor-associated macrophages is currently investigated. Most of our experiments rely on the use
of powerful and original approaches: confocal and two-photon microscopy as well as a preparation of tissue slices kept in live.
Magnus Essand, Ph.D., Professor, Immunology, Genetics and Pathology, Uppsala University
The success of CD19 CAR T-cells in treatment of B-cell malignancies has led to hopes that CAR T-cells may also be used to treat solid tumors. The main challenges though are lack of specific and uniformly expressed target antigens and an immunosuppressive
microenvironment found in most solid tumors. This presentation will discuss approaches to generate CAR T-cells able to resist immunosuppression and activate bystander effector cells to kill antigen-negative tumor cells.
16:05 CAR T Cell Immunotherapy of Solid Tumors and Hypoxia Induced Escape Mechanisms
Soldano Ferrone, M.D., Ph.D., Division of Surgical Oncology, Surgery, Massachusetts General
Hospital and Harvard Medical School
Hypoxia induces changes in T cells and target cells. These changes lead to the development of escape mechanisms utilized by tumor cells to avoid immune recognition and destruction. These escape mechanisms will be described. In addition, the
strategies developed to counteract these escape mechanisms will be discussed.
16:35 End of Conference
Day 1 | Day 2 | Speaker Biographies | Download Brochure