Cambridge Healthtech Institute’s 5th Annual
Engineering Next-Generation Cancer Immunotherapies
New Protein Engineering Science and Technology to Support the Development of Novel Immunotherapeutics and Treatment Combinations
January 14-15, 2019
It has now been seven years since the first approval of ipilimumab, and there are now six mainstream checkpoint inhibitors approved for a range of cancers. Based on these clinical successes, the industry is now directing its attention to combination treatments,
single agent therapeutics with multiple modes of action, confronting resistance mechanisms, reducing toxicity and the persistent challenge of solid tumors. Cambridge Healthtech Institute’s 5th Annual Engineering Next-Generation Cancer Immunotherapies
provides a forum in which research scientists can discuss the contributions of protein engineering to the discovery and development of novel biotherapeutics in the oncology space.
Final Agenda
SUNDAY, JANUARY 13
4:00 - 6:00 pm Pre-Conference Registration (Sapphire West Foyer)
MONDAY, JANUARY 14
7:00 am Registration and Morning Coffee (Sapphire West Foyer)
9:00 Welcome by Conference Organizer
Kent Simmons, Senior Conference Director, Cambridge Healthtech Institute
9:05 Chairperson’s Opening Remarks
John Williams, PhD, Professor, Department of Molecular Medicine, Beckman Research Institute; Member, Cancer Immunotherapeutics Program, City of Hope Comprehensive Cancer Center
KEYNOTE PRESENTATION
9:10 Advancing Development of Effective Immunotherapies – Therapeutic Modality Selection and the Tumor Microenvironment
Gary C. Starling, PhD, AVP, Protein Science Merck
With the recent advances in cancer immunotherapy, it is evident that the antigen-specific activation of the patients’ immune responses can be utilized for achieving significant therapeutic benefits. Despite the success of monoclonal antibodies against immune checkpoints, other therapeutic modalities are being applied to address many challenges of the biology of the tumor microenvironment. The potential of these agents as monotherapy or in combination with immune checkpoint inhibitors will be highlighted.
9:50 T Cell Engaging Bispecific Antibodies: Comparing Pfizer’s Platforms
Javier Chaparro-Riggers, PhD, Senior
Director, Protein Engineering, Pfizer
T cell engaging bispecific antibodies are a promising therapeutic approach for the treatment of multiple cancer types. A variety of formats are currently being tested in the clinic. Pfizer has developed several Fc-containing T cell engaging bispecific
antibody platforms that increase the half-life and allow for conventional dosing. These platforms are currently evaluated in the clinic. Here, we will compare these platforms and the challenges and opportunities of each platform will be highlighted.
10:20 Networking Coffee Break (Sapphire & Aqua West Foyer)
10:45 Development and Validation of Imaging Biomarkers for IO Applications
Michael Evans, PhD, Assistant Professor, Radiology and Biomedical
Imaging, University of California, San Francisco
This presentation will outline recent efforts at UCSF to apply omics technologies and phage display to identify and target with recombinant human antibodies cell surface antigens that are upregulated by important oncogenic drivers. Recent screening
efforts have identified new antibodies against cell surface proteins upregulated by mutant KRAS, c-MYC, and mTORC1, and the antibodies have been further matured for nuclear medicine applications like PET imaging and radioimmunotherapy.
11:15 Development of a New Patient Derived Xenograft Humanized Mouse Model to Study Human Specific Tumor Microenvironment and Immunotherapy
Qingfeng Chen, PhD, Principal Investigator, Institute of
Molecular and Cell Biology, A*STAR, Singapore
Recently, we transplanted patient-derived xenograft tumors with type I human leukocyte antigen-matched human immune system in NOD-scid Il2rg-/- mice. Similar to patients, the human immune system in our model is educated by tumor and exhibits exhaustion
phenotypes. Our model also demonstrates both therapeutic and side effects of immune checkpoint inhibitors. Thus, we provide a model for immune-oncology study and a useful parallel-to-human platform for anti-HCC drug testing, especially immunotherapy.
11:45 Pritumumab, the Journey from the Bench to the Bedside
Mark C. Glassy, PhD, CSO, Nascent Biotech
Pritumumab, a natural human IgG1 kappa antibody recognizes an altered form of vimentin called ecto-domain vimentin (EDV) expressed on the surface of cancer cells. In a Phase II clinical trial with Japanese brain cancer patients, pritumumab showed
an overall response rate of 25-30%. A recombinant version of pritumumab was made from CHO cells and is currently being prepared for additional FDA-approved clinical trials.
12:15 pm Creating the Imperfectly Perfect 3D Tumor Models: Data to Delivery
Prabuddha Kundu, Cofounder & Managing Director, Premas Biotech Pvt Ltd
12:45 Session Break
12:55 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
2:00 Chairperson’s Remarks
Yariv Mazor, PhD, Senior Scientist, Antibody Discovery & Protein Engineering, MedImmune, LLC
2:05 Checkpoint Inversion by INBRX-105: A Bispecific Multivalent PD-L1 x 41BB Single Domain Antibody Therapeutic Delivering Checkpoint Blockade and Conditional Immune Activation within the Tumor
John Timmer, PhD, Vice President, Research, InhibRx
InhibRx has developed a bispecific multivalent antibody with conditional 41BB agonist activity and potent PDL1 checkpoint blockade. This checkpoint inversion converts T cell suppressive PDL1 within the tumor into 41BB agonism driving anti-tumor T cell
co-stimulation while avoiding toxicity from systemic 41BB activation. INBRX-105 is built from InhibRx’s proprietary single domain antibody platform and innovative therapeutic format. Potent preclinical efficacy combined with a clear safety profile
have propelled INBRX-105 toward the clinic.
2:35 Development of the First Enzyme-Based Immune Checkpoint Inhibitor for Cancer Therapy
Christos Karamitros, PhD, Director, Protein
Engineering, Aeglea Biotherapeutics
It is well established that kynurenine, a key intermediate metabolite of the tryptophan catabolic pathway, has very potent immunosuppressive properties. Current clinical approaches focus on the development of IDO1 and TDO inhibitors to impair kynurenine
synthesis. However, our novel approach degrades kynurenine into non-toxic and immunologically inactive metabolites in order to relieve immune suppression in cancer. This work showcases the first enzyme-based immune checkpoint inhibitor.
3:05 Find Your Table and Meet Your BuzZ Session Moderator
3:15 BuzZ Sessions with Refreshments (Sapphire & Aqua Foyer)
Join your peers and colleagues for interactive roundtable discussions.
Click here for more details
4:30 Design Meets Biology – Engineering a PD-1/CTLA-4 Bispecific Antibody to Improve Both Safety and Efficacy
Yariv Mazor, PhD, Senior Scientist, Antibody Discovery &
Protein Engineering, MedImmune, LLC
MEDI5752 is a monovalent bispecific IgG1 antibody (DuetMab), targeting the two clinically validated receptors; PD-1 and CTLA-4. The bispecific antibody introduces novel MOAs that may provide an improved therapeutic index when compared to the two
monotherapies and mAb combinations. MEDI5752 is currently being clinically evaluated for safety and efficacy.
5:00 Functionalization of mAbs Using Natural Amino Acids
John Williams, PhD, Professor, Department of Molecular Medicine, Beckman Research Institute; Member, Cancer Immunotherapeutics Program, City of Hope Comprehensive Cancer Center
Many disparate genetic and chemical approaches have been developed to leverage the exquisite specificity of antibodies for therapeutic and diagnostic intent. Here, we use the site-specific meditope interaction to catalyze the efficient formation
of a disulfide bond without the need for incorporating non-natural amino acids or post-translational, enzymatic modifications. This ‘swappable’ platform permits the stable modification of antibodies through the exchange of meditopes
functionalized to include imaging agents, cytotoxins and biologics.
5:30 Tumor Antigen-Dependent T Cell Activation and Tumor Localization Induced by a Novel 4-1BB x 5T4 ADAPTIR™ Bispecific Antibody
Sara Fritzell, PhD, Senior Scientist, Alligator
Bioscience AB, Sweden
ALG.APV-527 is designed to induce potent tumor specific CD8 T cell activation by activating 4-1BB on T cells only when simultaneously engaging 5T4 on tumor cells. Pre-clinical in vitro and in vivo data demonstrates that ALG.APV-527 stimulates increased T cell activation in the presence of 5T4-expressing cells, localizes to 5T4 positive tumors and inhibits tumor growth. This data supports its potential to provide effective tumor-directed
immune activation with reduced systemic side effects.
6:00 - 7:15 Welcome Reception in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
7:15 Close of Day
TUESDAY, JANUARY 15
8:00 am Registration and Morning Coffee (Sapphire West Foyer)
8:45 Chairperson’s Remarks
Peter Ellmark, PhD, Vice President, Discovery, Alligator Bioscience AB, Sweden
8:50 Application of Single Domain Antibody Technology in CAR-T Cells for Treating Solid Tumors
Mitchell Ho, PhD, Senior Investigator, National Cancer Institute, NIH
Single domain antibodies represent a very different class of molecules: small, easy to express, stable and capable of revealing buried epitopes unreachable by conventional antibodies. We have generated single domain antibodies that target tumor antigens
(e.g. mesothelin, GPC3 and GPC2) and developed CAR T cells based on these antibodies. Construction and next-generation sequencing analysis of our new phage-displayed shark and camel single domain antibody libraries will also be described.
9:20 CAR-Ts and Combination Therapy with Checkpoint Blockade
Prasad S. Adusumilli, MD, Head, Solid Tumors Cell
Therapy, Cellular Therapeutics Center (CTC), Memorial Sloan-Kettering Cancer Center
In solid tumor immunotherapy, we have shown that regional administration of CAR T cells will have increased potency and decreased toxicity, and that exhausted PD-1 expressing CAR T cells can be functionally rescued by use of checkpoint blockade agents.
We now have translated both concepts to clinical trials. The specifics of patient stratification for combination immunotherapy, evaluation parameters and outcomes interpretation are ongoing areas of clinical and translational investigation.
9:50 Coffee Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
11:00 Rewiring T Cell Responses to Soluble Factors with Chimeric Antigen Receptors
Yvonne Chen, PhD, Assistant Professor, Chemical & Biomolecular
Engineering, UCLA
Immunosuppression in the tumor microenvironment presents a critical barrier to chimeric antigen receptor (CAR)-T cell therapy for solid tumors. Here, we discuss the development of CARs that respond to soluble antigens in general and the immunosuppressive
cytokine TGF-β in particular. The development of CAR-T cells that can convert soluble immunosuppressive factors into potent T cell stimulants offers a new approach to engineering effective CAR-T cell therapies for solid tumors.
11:30 Development of a Universal CAR-T Cell Targeting System
Mauro Castellarin, PhD, Postdoctoral Researcher,
Center for Cellular Immunotherapies, University of Pennsylvania School of Medicine
CAR T cell (CART) targeting of solid tumors is hindered by heterogeneous tumor clones with diverse antigen profiles. To counter this, we developed a universal CAR that can attach to different antigen recognition molecules and enables CARTs to kill
a diverse set of tumor cells. This is a promising new advancement as it allows CART treatment to adapt to changes in the tumor landscape throughout the course of the disease.
12:00 pm Sponsored Presentation (Opportunity Available)
12:30 Session Break
12:40 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:10 Close of Engineering Next-Generation Cancer Immunotherapies Conference
5:45 - 8:45 Recommended Dinner Short Courses*
SC1: Introduction to CAR-T Engineering for Protein Scientists - Detailed Agenda
SC2: Structure-Based Optimization of Antibodies
SC4: Immunogenicity for Biologics
Click here for more details.
*Separate registration required