Cambridge Healthtech Institute’s Fourth Annual

Engineering Next-Generation Cancer Immunotherapies

New Protein Engineering Science and Technology to Support the Development of Novel Immunotherapeutics and Treatment Combinations

January 8-9, 2018

 

A succession of strong clinical successes with antibodies against checkpoint targets has spawned a surge of interest from across the industry in the development of antibody immunotherapeutics and treatment combinations. The major challenges facing those now entering the field include establishing clinical proof of concept, product and target differentiation, selection of patient responders and the rational design of effective immunotherapy combinations. Cambridge Healthtech Institute’s Fourth Annual Engineering Next-Generation Cancer Immunotherapies offers presentations of protein engineering strategies to improve the efficacy of immunotherapeutics and drive the progress of more personalized treatments in this space.

SUNDAY, JANUARY 7

4:00 - 6:00 pm Pre-Conference Registration

MONDAY, JANUARY 8

7:00 am Registration and Morning Coffee

Antibody Engineering Challenges for Immunotherapeutics

9:00 Welcome by Conference Organizer

Kent Simmons, Senior Conference Director, Cambridge Healthtech Institute

9:05 Chairperson’s Opening Remarks

Dimiter S. Dimitrov, Ph.D., Professor of Medicine and Director, Center for Antibody Therapeutics, University of Pittsburgh Medical School

KEYNOTE PRESENTATION

9:10 Evolution and Advancements in Cancer Immunotherapy

Partha_ChowdhuryPartha Chowdhury, Ph.D., Senior Director and Head, Antibody Discovery, Sanofi Genzyme

Cancer is an immunological disease characterized by hijacking and evasion of the natural immune response of the host. Although the idea to exploit the host’s immune response to fight against cancer is decades old, clinical success of immunotherapy is a relatively new achievement. This talk will focus on the various strategies used to manipulate a multitude of factors that underlies the phenomenon of immunotherapy, including recent advancements on new targets and approaches to enhance the therapeutic efficacy of novel biological drugs.

9:50 Tumor-Activated Checkpoint Inhibitors

John C. Williams, PhD, Professor, Department of Molecular Medicine; Co-Director, Drug Discovery and Structural Biology, Beckman Research Institute at City of Hope

Targeting immune checkpoints is rapidly changing the clinical management of a growing list of tumor entities. However, checkpoint therapy is encumbered by immune-related adverse events (irAEs), which can be severe. We present our engineering efforts to reduce irAEs, demonstrating the localized activity of murine checkpoint surrogates effectively eliminates in vivo tumor growth while markedly reducing activation of regulatory T cells in healthy tissue.

10:20 Networking Coffee Break

10:45 The Impact of mAb Format in Targeting the Tumor Microenvironment

Stephen_BeersStephen Beers, Ph.D., Associate Professor, Cancer Immunology and Immunotherapy, University of Southampton, United Kingdom

Monoclonal antibodies (mAb) are transforming cancer therapy. Although the number of mAb reaching the clinic continues to rise rapidly, successful targets are scarce and new ones frequently fail. Understanding why promising pre-clinical candidates do not translate to humans is a critical question. Here we show how mAb format can be key to efficacy and that this could be particularly relevant when seeking new mAb to target the tumor microenvironment.

11:15 Novel Therapeutic Antibodies for Cancer Isolated from Single Human B Cells

Edward_PatzEdward F. Patz, Jr., M.D., Professor, Radiology, Pharmacology and Cancer Biology Duke University Medical Center

In an effort to develop novel therapeutic antibodies, we took cues from the native immune response in “exceptional outcomes” patients. We identified relevant tumor antigens by exploring the humoral response against the tumor, and then isolated and expressed DNA sequences from the relevant single B cells. A recombinant antibody was produced, and showed anti-tumor activity. This strategy represents an alternative paradigm in anti-cancer drug discovery.

11:45 Manipulation of Affinity Maturation and B Cell Subsets in vivo

Ali_ZarrinAli Zarrin, Ph.D., Senior Scientist, Immunology and Antibody Engineering, Genentech

B cells diversify their immunoglobulin genes to produce high affinity antibodies. Antigen specific B cells are selectively differentiated in the germinal centers to seed short- or long- lived plasma cells, a process known as affinity maturation. It is not clear how B cells commit to short or long-lived plasma cell fate. Our study provides insights on how this decision might be made during immune response and autoimmunity.

12:15 pm Antigen Epitope Analysis and De-Immunogenicity of Antibody/Protein Drugs

Le Sun, Ph.D., CEO, AbMax Biotechnology

The presentation will describe the prediction of immunogenicity based on a.a. sequence using B-cell epitope analysis and explore the strong correlations of ADA data between animal studies and human clinic trials. We will also present a case study with de-immunogenicity of Humira showed that ADA titers in mouse were reduced by 90%.

12:45 Enjoy Lunch on Your Own

Immunotherapy Combinations

2:00 Chairperson’s Remarks

Stephen Beers, Ph.D., Associate Professor, Cancer Immunology and Immunotherapy, University of Southampton, United Kingdom

2:05 Update on Clinical Progress of Immunotherapy Combinations

Gregory Daniels, M.D., Ph.D., Professor, Medicine, Moores Cancer Center, University of California, San Diego

Tumors development occurs in the context of a functioning immune system with intrinsic and extrinsic growth pathways dynamically shaping a pro-tumor microenvironment. Tumor response to current therapies depend upon the quantitate and qualitative presence of the natural immune response. I will discuss examples of combination immune therapy in solid tumors that overcome the barriers in generating an anti-tumor response.

2:35 Rational Combination of Oncolytic Virus and Checkpoint Therapy

Jason DeVoss, Ph.D., Senior Scientist, Oncology, Amgen

3:05 Transition to BuzZ Sessions

3:15 BuzZ Sessions with Refreshments

Join your peers and colleagues for interactive roundtable discussions.

Emerging Pathways and Targets for Cancer Immunotherapy

4:30 Targeted Mass Spectrometry for Cancer Antigen Discovery

Paul_ArmisteadPaul Armistead, M.D., Ph.D., Associate Professor, Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill

Mass spectrometry based identification of HLA-bound, cancer antigens is essential for many immunotherapeutic strategies; however, standard non-targeted methods are insensitive and inadequate for the discovery of previously undefined peptides (e.g., neoantigens). These problems can be overcome, however, by optimizing mass spectrometers for the targeted detection of specific antigens. Targeting approaches that we have adopted involve differential ion mobility spectrometry for target enrichment and parallel reaction monitoring for target confirmation.

5:00 The Importance of Fc Receptor Interactions for OX40 Agonists and Their Ability to Drive Tumor Ag-Specific T Cell Expansion

Andrew_WeinbergAndrew Weinberg, Ph.D., Judy Ann Hartmann Endowed Chair for Cancer Immunology Research, Robert W. Franz Cancer Research Center

OX40 agonists have been shown to increase T cell effector function, proliferation and survival. These T cell stimulating properties are important to enhance anti-tumor therapeutic efficacy. We have found that Fc receptor interactions are important for the agonist properties of these OX40 targeting Abs, which appear to be completely independent of Treg depletion. Recently we have found that OX40 agonists can expand tumor reactive T cells within the cancer microenvironment.

5:30 End of session; delegates may attend concurrent programming.

 

Nanotemper Technologies6: 00 - 7:15 Welcome Reception in the Exhibit Hall with Poster Viewing

7:15 Close of Day

TUESDAY, JANUARY 9

8:00 am Registration and Morning Coffee

Novel Immunotherapies

8:30 Chairperson’s Remarks

G. Jonah Rainey, Ph.D., Executive Director, Research, MabVax Therapeutics Holdings, Inc.

8:35Pritumumab, the First Therapeutic Antibody for Glioma Patients

Mark C GlassyMark C Glassy, PhD, Chairman, Nascent Biotech; Visiting Scholar, Translational Neuro-Oncology, Moores Cancer Center, University of California, San Diego

Gliomas are a particularly aggressive form of brain cancer for which immunotherapy may hold promise. Pritumumab is a natural human IgG1kappa monoclonal antibody developed from a B lymphocyte isolated from a regional draining lymph node of a patient with cervical carcinoma. Here we review data on the development and characterization of Pritumumab, and review clinical trials data assessing immunotherapeutic effects of Pritumumab for glioma patients.

 

9:05Efficacy of CAR-T Cells and Other Immunotherapies

Dimiter_DimitrovDimiter S. Dimitrov, Ph.D., Professor of Medicine and Director, Center for Antibody Therapeutics, University of Pittsburgh Medical School

Parameters that could affect efficacy of CAR-T cells and other immunotherapies including affinity, epitope location, surface expression and concentration of target cell surface associated antigen will be discussed as well as possible underlying mechanisms. Specific examples will be presented including an update on the high efficacy of the anti-CD22 CARs based on the scFv m971 as well as newly developed BiKEs targeting the HIV-1 envelope glycoprotein.

9:35 Featured Poster Presentation: Identification of Breast Cancer Subtype-Specific Biomarkers by Phenotypic Selection

Kristine_KimKristine Kim, PhD, Professor, Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Korea

For the discovery of diagnostic and therapeutic targets, we have developed a systematic approach for concurrent identification of Ab/Ag pairs. In this presentation, the technical platform for the discovery of Ab/Ag pairs for molecular subpopulation of breast cancers including an example for their potential value for diagnostic and therapeutic biomarkers will be presented.

9:50 Coffee Break in the Exhibit Hall with Poster Viewing

11:00 A New Immunomodulatory Strategy of Releasing Immunosuppression in the Tumor Microenvironment

Carolyn_BertozziCarolyn R. Bertozzi, PhD, Professor, Chemistry, Howard Hughes Medical Institute, Stanford University

Cancer therapy has been revolutionized by inhibiting immune-checkpoints to harness the power of the immune system in fighting cancer. Immune-checkpoint inhibitors have proved to achieve a durable response in a subset of cancer patients. However, most patients are still resistant to these first generation I/O drugs. Enormous effort is pursued to identify new immunomodulatory strategies. We describe a novel approach of blocking an immunosuppression pathway involved in innate and adaptive response.

11:30 Achieving Broad Tumor Coverage by Targeting Cancer Carbohydrate Antigens: Lessons from the Clinic Accelerate Development of Additional Targets

Jonah_RaineyG. Jonah Rainey, Ph.D., Executive Director, Research, MabVax Therapeutics Holdings, Inc.

Glycans are promising therapeutic targets present on broad tumor types. We are clinically developing an anti-sialyl Lewis A (sLea) naked antibody (MVT-5873), immunoPET imaging agent (MVT-2163), and radioimmunoconjugate (MVT-1075). Here we describe a fully human antibody against another cancer glycan, Tn (GalNAc alpha-O-Ser/Thr), which shows minimal overlap with sLea by tumor microarray. We compare translational learnings from anti-sLea programs and describe how they have guided development of our anti-Tn effort.

12:00 pm Featured Poster Presentation: Engineering Adenosine Deaminase 2 for Cancer Immunotherapy Development

Lin_WangLin Wang, Ph.D., Principal Scientist, Halozyme Therapeutics, Inc.

Adenosine is an endogenous immunosuppressant that binds to adenosine receptor checkpoints. Abnormally high level of adenosine contributes to a highly immunosuppressive tumor microenvironment (TME). We hypothesized that adenosine deaminase 2 (ADA2), a human enzyme that catalyzes the deamination of adenosine, could be administered at therapeutic levels to deplete high level of TME adenosine and stimulate anti-tumor immune activity. This talk will present data that supports our hypothesis.

12:30 Session Break

12:45 Luncheon Presentation: Identification of Novel Receptor Targets and Specificity Screening of Biotherapeutics

Alex_KellyAlex Kelly, Business Development Manager, Retrogenix Limited

Human cell microarray screening enables the discovery of primary cell surface receptors and off-targets for a variety of biotherapeutic molecules, including peptides, antibodies and proteins, as well as CAR T and other cell therapies. Case studies will demonstrate the utility of the technology in identifying novel immunotherapy targets as well as in specificity screening for biotherapeutics to aid safety assessment and provide critical data to support IND submissions.

1:15 Close of Engineering Next-Generation Cancer Immunotherapies Conference


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