Cambridge Healthtech Institute’s Third Annual
Engineering Next-Generation Cancer Immunotherapies
New Science and Technologies for Protein Engineers and Discovery Scientists
to Support Development of Novel Immunotherapeutics and Treatment Combinations
January 9-10, 2017 | Hilton San Diego Bayfront | San Diego, CA
A succession of strong clinical successes by antibody therapeutics against the mainstream checkpoint targets has spawned a surge of interest from across the industry in advancing novel immunotherapeutics and agents that perform well in treatment combinations.
Cambridge Healthtech Institute’s Third Annual Engineering Next-Generation Cancer Immunotherapies meeting offers important updates on scientific strategies and technologies that will be used by protein engineers and discovery scientists to support
the development of the next wave of highly efficacious cancer immunotherapies.
MONDAY, JANUARY 9
7:30
am Conference Registration and Morning Coffee
9:00 Welcome by Conference Organizer
Kent Simmons, Senior Conference Director, Cambridge Healthtech Institute
9:05 Chairperson’s Opening Remarks
Kris F. Sachsenmeier, Ph.D., Associate Director, Translational Sciences, AstraZeneca
Keynote Presentation
9:10 An NIH Perspective on Emerging Target Classes for Cancer Immunotherapy
Mitchell Ho, Ph.D., Senior Investigator and Chief, Antibody Therapy Section, Laboratory of Molecular Biology, National
Cancer Institute, NIH
Antibodies have a major role in cancer treatment. To increase their efficacy, we need to design them to inhibit signaling pathways responsible for the growth of cancer. This can be done by decreasing the size of the antibody so it can target cryptic
or buried functional regions in receptors or signaling complexes. Another need is to identify new therapeutic targets in cancer and make antibodies that modulate their activity.
9:50 ADAPTIR™ Bispecifics, a Novel Platform for Development of Immuno-Oncology Therapeutics
John Blankenship, Ph.D., Lead Scientist, Molecular Biology and Protein Engineering, Aptevo Therapeutics
Bispecific T-cell engagers, an emerging technology, have received attention from the approval of BLINCYTO™ (blinatumomab) targeting CD19/CD3 for treatment of ALL. The ADAPTIR™ platform is a novel technology with improved characteristics
that address concerns around stability, manufacturability and half-life of bispecifics, while retaining potent and distinct preclinical activity. The ADAPTIR platform is being used to develop bispecifics that mediate T-cell engagement and bispecifics
with new mechanisms of action in immune-oncology.
10:20 Coffee
Break
10:45 Emerging Predictive Biomarkers for Cancer Immunotherapy
Sandip P. Patel, M.D., Assistant Professor, Cancer Immunotherapy Program, Experimental Therapeutics, Thoracic Oncology,
Moores Cancer Center, University of California, San Diego
The advent of cancer immunotherapy has revolutionized oncology. With a growing pipeline of therapeutic targets, the need for predictive biomarkers to optimize immunotherapeutic regimens is of increasing importance. This presentation will review novel
immunotherapeutic biomarker assays and their role in the clinic.
11:15 Hexavalent Single-Chain TNFSF-RBD-FC Fusion Proteins for Cancer Immunotherapy
Oliver Hill, Ph.D., Vice President, Molecular Biology Apogenix AG
TNFRSF targeting compounds with a solely agonistic activity on immune cells are still rare. Apogenix’s single-chain-based fusion proteins mimic the three-dimensional organization of the natural ligands (the TNFSF-proteins). In contrast to antibodies,
their agonistic activity does not rely on secondary crosslinking events in vitro nor in vivo. We will present the molecular engineering concept and the current results obtained
for the TRAIL-R-, CD40-, GITR-, HVEM- and CD27-agonists.
11:45 New Pathways for T Cell Costimulation and Coinhibition
Xingxing Zang, MMed, Ph.D., Miriam Mandel Faculty Scholar in Cancer Research Associate Professor, Microbiology
& Immunology, Albert Einstein College of Medicine
CTLA-4 and the PD-1/PD-L1 pathway are current focuses in cancer immunotherapy. This presentation will discuss other new immune checkpoints for future human cancer immunotherapy.
12:15
pm Cancer Biotherapeutics - Affimers: A Novel Scaffold for Biotherapeutics
Amrik Basran, 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.
12:45 Session Break
1:00 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
2:00 Chairperson’s Remarks
John Desjarlais, Ph.D., CSO, Xencor
2:05 Mechanisms of Action for the Application of BiTE Antibodies in Immunotherapy Combinations
Tara Arvedson, Ph.D., Director, Oncology Research, Amgen
Recent clinical data have demonstrated the potency and significance of T-cells in anti-tumor activity. For example, the CD19/CD3 bispecific T-cell engager (BiTE®) blinatumomab is now a proven means of harnessing T-cells for the treatment of cancer,
and a CD33/CD3 BiTE is currently in clinical development. This presentation will cover mechanisms of action for BiTE® molecules and the potential for immunotherapy combinations.
2:35 Bispecific Antibodies for T-Cell Redirection and Dual Checkpoint Blockade
John Desjarlais, Ph.D., CSO, Xencor
We have optimized a plug-and-play, Fc-containing bispecific antibody platform with high stability, efficient production, and antibody-like pharmacokinetics. This optimized bispecific format resembles a standard monoclonal antibody, with one of the
Fab arms replaced by a stability-optimized single-chain Fv (scFv) (scFv-Fab-Fc). We will present application of the platform to create a pipeline of CD3 bispecifics for T-cell redirection, and dual checkpoint blockade bispecifics for T-cell activation.
3:05 Featured Poster Presenter: Engineered Fc Variants with Selectively-Enhanced Binding to FcγRIIb for Various Applications
Hitoshi Katada Ph.D., Research Scientist, Research Division, Chugai Pharmaceutical Co. Ltd.
We have developed various platforms of engineered Fc variants with highly selective binding to FcγRIIb, which is named as TwoB-Ig. This unique selectivity enables to exploit FcγRIIb for various applications without eliciting undesired
immune response. In this presentation, in vitro and in vivo data for the application of TwoB-Ig technology to improve pH-dependent antigen binding antibody and enhance agonistic activity of anti-TNFR antibody will be presented.
3:20 Refreshment Break in the Exhibit Hall with Poster Viewing
4:00 Co-inhibition of CD73 and A2AR Adenosine Signaling Improves Anti-tumor Immune Responses
Kris F. Sachsenmeier, Ph.D., Associate Director, Translational Sciences, AstraZeneca
Co-blockade of the ectonucleotidase that generates adenosine CD73 and the A2A adenosine receptor that mediates adenosine signaling in leuokocytes. Using compound gene-targeted mice or therapeutics that target these molecules, tumor initiation,
growth, and metastasis were limited. This tumor control requires effector lymphocytes and interferon-g, while antibodies targeting CD73 promote an optimal therapeutic response in vivo when engaging activating Fc receptors. In a two-way mixed
leukocyte reaction using a fully human anti-CD73, we demonstrated that Fc receptor binding augmented the production of proinflammatory cytokines.
4:30 Chemically Programmed Bispecific Antibodies
Christoph Rader, Ph.D., Associate Professor, Cancer Biology and Molecular Therapeutics, The Scripps
Research Institute
Chemically programmed bispecific antibodies (cp-biAbs) endow tumor-targeting small molecules with the ability to recruit and activate T cells for selective and potent killing of tumor cells. We merged two different clinically translated antibody
technologies to generate a novel cp-biAb platform and demonstrated its utility for cancer therapy in vitro and in vivo. Thus, our technology provides tumor-targeting compounds
access to the power of cancer immunotherapy.
5:00 Combination Therapy of CAR T-Cells and Checkpoint Blockade
Prasad S. Adusumilli, M.D., FACS, Deputy Chief, Thoracic Service, Memorial Sloan Kettering Cancer
Center
Adaptive resistance developed by the solid tumors following immune attack poses a hurdle for achieving durable responses by both CAR T-cell therapy and checkpoint blockade. We have shown that the effector function of CAR T-cells was restored through
PD-1 antibody checkpoint blockade or with cell-intrinsic PD-1 blockade mediated by shRNAs or a dominant negative receptor. These findings provide a translatable strategy for combining CAR therapy and PD-1/PD-L1 blockade.
6:20-7:30 Welcome Reception in the Exhibit Hall with Poster Viewing
7:30 Close of Day
TUESDAY, JANUARY 10
8:00
am Conference Registration and Morning Coffee
8:30 Chairperson’s Remarks
Dimiter S. Dimitrov, Ph.D., Senior Investigator, Protein Interactions Section, Cancer and Inflammation Program, National Cancer Institute, NIH
8:35 The 2.3 Angstrom Structure of Pembrolizumab, a Full-Length Anti-PD1 Therapeutic IgG4 Antibody
Giovanna Scapin, Ph.D., Principal Scientist, Structural Chemistry, Merck & Co., Inc.
The structure of Pembrolizumab shows that it is a compact molecule, with one of the Fc CH2 domains rotated about 120 degrees with respect to the position observed in other structures. This novel conformation is possibly driven by the shorter
and more constrained IgG4 hinge. The structure suggests a role for the S228P mutation in preventing arm exchange, and may explain some specific characteristics of the IgG4 subclass.
9:05 Affinity and Epitope Interplay in Antibody Efficacy
Dimiter S. Dimitrov, Ph.D., Senior Investigator, Protein Interactions Section, Cancer and
Inflammation Program, National Cancer Institute, NIH
The antibody affinity could correlate with efficacy, but in many cases, its epitope is critical. The dependence of efficacy on affinity/avidity and epitope is complex and affected by the antibody format and target properties including
surface concentration. Several examples of the important role of the antibody epitope for efficacy will be discussed including our antibodies against CD22 and folate receptor beta.
9:35 Featured Poster Presentation: Enhancing the Anti-Leukemia Functions of Invariant Natural Killer T cells Using a Tumor Antigen-Specific Model
Rupali Das, Ph.D., Assistant Professor, Physiology, Michigan State University
9:50 Coffee Break in the Exhibit Hall with Poster Viewing
11:00 Functionalization of Monoclonal Antibodies Using Mechanical Bonds
John Williams, Ph.D., Professor, Molecular Medicine, Director, X-Ray Core Facility, Beckman Institute,
City of Hope
Through diffraction studies and rational design efforts, we have significantly improved the affinity of the meditope interaction, enabling us to thread an azide through the Fab hole and use click chemistry to create a mechanical bond.
Offering an efficient and rapid means to functionalize meditope-enabled mAbs, we will present recent data using mechanical bonds including imaging and novel BiTE approaches for immunotherapy
11:30 Improving Immunotherapy with the HexaBody Platform
Paul W.H.I. Parren, Ph.D., Senior Vice President & Scientific Director, Genmab
Monomeric IgG antibodies organize into ordered hexamers after binding their cognate antigen expressed on a cell-surface. This process is dependent on specific Fc:Fc interactions located in the interface between neighboring IgG molecules
in the hexamer. Based on this concept, we developed the HexaBody technology to generate potentiated antibody therapeutics. Their ability to induce improved cell killing when used alone or in combination will be discussed.
12:00 pm Sponsored Presentation (Opportunity Available)
12:30 Session Break
12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:15 Close of Conference