ABC


The outlook for antibodies against oncology targets is exploding with the discovery of novel targets and the ability to effectively modulate the immune system. This meeting will investigate current trends in identifying, validating and developing antibody drugs for oncology. We will highlight antibodies in clinical development, the advancement of novel constructs and identification of successful strategies in the use of antibodies for immunotherapy. Plan to attend to network and hear about exciting developments from leaders in the community.

Scientific Advisory Board

Soldano Ferrone, M.D., Ph.D., Division of Surgical Oncology, Surgery, Massachusetts General Hospital

John Haurum, M.D., CEO, F-star GmbH & F-star Biotechnology Ltd.

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

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MONDAY, APRIL 25

7:00 am Registration and Morning Coffee


Emerging Targets: Keynote Presentations

Keynote Presentations:

8:30 Chairperson’s Remarks

Mitchell Ho, Ph.D., Chief, Antibody Therapy Section, Laboratory of Molecular Biology, National Cancer Institute, NIH

8:40 IL-15 Augments Antibody-Dependent Cell-Mediated Cytotoxicity of Anticancer Monoclonal Antibodies

Thomas_WaldmannThomas A. Waldmann, M.D., Co-Chief, Lymphoid Malignancies Branch; Senior Investigator, Head, Cytokine Immunology and Immunotherapy Section, Center for Cancer Research, National Cancer Institute

In clinical trials IL-15 increased the number of activated NK cells and monocytes in patients with metastatic malignancy. In a preclinical syngeneic tumor model IL-15 dramatically increased the ADCC efficacy of rituximab in the treatment of the human CD20 expressing murine EL4 leukemia model. IL-15 also augmented efficacy of the combination of anti-CTLA-4 and anti-PD-L1 anti-checkpoint antibodies. These studies support the use of IL-15 in combination with anticancer monoclonal antibodies.

9:10 Therapeutic Targeting of Breast Cancer Stem Cells

Max_WichaMax S. Wicha, M.D., Madeline and Sidney Forbes Professor, Oncology; Founding Director Emeritus, University of Michigan Comprehensive Cancer Center

Tumor heterogeneity represents the greatest challenge to the development of effective cancer therapies. In addition to genetic heterogeneity, tumors are hierarchically organized and driven by subpopulations of cells that display stem cell properties. These “cancer stem cells” also mediate tumor metastasis and contribute to treatment resistance. Both small molecule and antibody based therapies have been developed to target cancer stem cell populations. The assessment of clinical efficacy of cancer stem cell therapeutics will require innovative clinical trial design. Progress in developing cancer stem cell therapeutics will be reviewed.

9:40 Emerging Targets in Pediatric Cancers

Javed_KhanJaved Khan, M.D., Deputy Chief, Genetics Branch; Senior Investigator, Head, Oncogenomics Section, National Cancer Institute

Despite improvement of survival rates in children with cancers over the past 20 years, patients with metastatic disease remain essentially incurable and novel therapies are required. I will describe strategies of using mRNA gene expression profiles to discover differentially expressed cell surface proteins in pediatric solid tumors. I will describe the Stand Up to Cancer St. Baldrick’s Immunogenomics Dream Team’s efforts to characterize the cell surfaceome of high risk pediatric solid cancers and to develop novel immunotherapeutic agents with a focus on targeting FGFR4.

10:10 Coffee Break


Emerging Targets (Cont.)

Chairperson’s Remarks

Mitchell Ho, Ph.D., Chief, Antibody Therapy Section, Laboratory of Molecular Biology, National Cancer Institute, NIH

10:50 Targeting Sleeping Cancer Cells

Sridhar_RamaswamySridhar Ramaswamy, M.D., Associate Professor, Medicine, Massachusetts General Hospital Cancer Center, Broad Institute, Harvard University and MIT

We recently discovered a b1-integrin/FAK/mTORC2/AKT1/TTC3-associated signaling pathway that is triggered by rapidly proliferating cancer cells to undergo asymmetric division and produce slowly proliferating AKT1low daughter cells that are highly resistant to chemotherapy in patients with a variety of solid tumor types. These findings reveal that proliferative heterogeneity within cancer cell populations is produced through a potentially targetable signaling mechanism, with implications for understanding cancer progression, dormancy, and therapeutic resistance.

Bispecific Antibodies and ADCs

11:20 Chairperson’s Remarks

Horacio G. Nastri, Ph.D., Senior Director, Antibody Biotherapeutics, Incyte Corporation

11:25 A Novel Auristatin-Based ADC that Targets PTK7

Marc_DamelinMarc Damelin, Ph.D., Associate Director, Oncology Research Unit, Pfizer, Inc.

PTK7 is a highly conserved, catalytically inactive kinase with oncogenic functions. We identified PTK7 by its enrichment on cancer stem cells, and we developed an auristatin-based anti-PTK7 ADC. The ADC induced sustained tumor regressions in preclinical tumor models and is currently in Phase I clinical testing. Two potential mechanisms that relate PTK7 to immuno-oncology will also be discussed.

11:55 Antibody-Drug Conjugates: Exploiting Differential Expression

Beverly_TeicherBeverly A. Teicher, Ph.D., Chief, Molecular Pharmacology Branch, National Cancer Institute

Antibody-drug conjugates (ADCs) offer a unique therapeutic approach for treatment of solid and hematologic malignancies. ADCs deliver a potent cytotoxic agent on the backbone of an antibody specifically targeted to malignant cells. This two-pronged approach is predicted to provide a more efficient manner to destroy tumor cells while sparing normal tissues. The road of ADCs into clinical practice has not been an easy one; however, recent results have been positive.

DiscoverX12:25 pm Enabling Development of Cancer Immunotherapy Drugs – From Discovery to Combination Strategies

Saharia_AbhiAbhi Saharia, Ph.D.,  Director, Cell-based Assays & Biologics,  DiscoverX Corporation

Developing drugs targeting checkpoint receptors and testing combinations in a pre-clinical setting can be challenging. Here, we discuss and demonstrate how DiscoverX technologies enable cancer immunotherapy development with assays for screening, lead optimization, efficacy testing, biomarker selection, and testing clinical combinations in a human tumor microenvironment.

 

12:40 Sponsored Presentation (Opportunity Available)

12:55 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:50 Session Break

2:20 Problem-Solving Breakout Discussions

Targeting Sleeping Cancer Cells

Sridhar Ramaswamy, M.D., Associate Professor, Medicine, Massachusetts General Hospital Cancer Center, Broad Institute, Harvard University and MIT

 

  • Quiescent cancer cells: Recent insights & advances
  • Therapeutic challenges in targeting sleepers
  • Clinical validation and trial design

Clinical Development Strategies for ADCs
Moderator: Marc Damelin, Ph.D., Associate Director, Oncology Research Unit, Pfizer, Inc.

  • What are some of the most exciting ADCs in early clinical development?
  • What are the most promising strategies for combination therapies with ADCs?
  • What have been the biggest obstacles to clinical development of ADCs? How can these lessons inform current clinical strategies as well as selection of new targets?

 

3:20 Refreshment Break in the Exhibit Hall with Poster Viewing


PLENARY KEYNOTE SESSION

4:00 Chairperson’s Remarks

4:10 The Promise of Cancer Immunotherapy: An Overview of Recent Advances and Jounce’s Approach to Delivering the Right Therapy to the Right Patient

Deborah_LawDeborah Law, D. Phil. CSO Jounce Therapeutics, Inc.

As immunotherapies become an increasingly important component of cancer treatment the challenge will be to identify ways to provide the best therapy(s) to the individual. This presentation will provide an overview of current cancer immunotherapies as well as highlight some of the challenges ahead including selection of optimal combinations, moving outside of T cell-directed approaches, and will highlight how Jounce Therapeutics is using its Translational Science Platform as an approach to develop and deliver the right therapy to the right patient.

4:50 Antibody as Drugs: Then, Now and Tomorrow

Paul_CarterPaul J. Carter, Ph.D., Senior Director and Staff Scientist, Antibody Engineering, Genentech

Antibodies have grown into a clinically and commercially important drug class with more than >45 antibodies marketed for imaging or therapy in the USA and/or Europe and with ~$63 billion in worldwide sales in 2013.  This presentation will highlight progress in developing antibody drugs and consider opportunities for future innovation.  


5:30 Welcome Reception in the Exhibit Hall with Poster Viewing

6:45 End of Day

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TUESDAY, APRIL 26

8:00 am Morning Coffee


Intracellular Antigens Recognized by Monoclonal Antibodies

8:25 Chairperson’s Remarks

Soldano Ferrone, M.D., Ph.D., Division of Surgical Oncology, Surgery, Massachusetts General Hospital

8:30 Intracellular Tumor Antigens as a Source of Targets for Antibody-Based Immunotherapy of Solid Tumors

Soldano_FerroneSoldano Ferrone, M.D., Ph.D., Division of Surgical Oncology, Surgery, Massachusetts General Hospital

It is generally assumed that to be recognized by an antibody in viable cells, the antigen has to be expressed on the plasma membrane of malignant cells. In this study we challenge this assumption and we show that the monoclonal antibody (mAb) W9, isolated from a phage human antibody library, recognizes an extracellular epitope of the chaperone molecule Grp94, which is located in the endoplasmic reticulum. mAb W9 recognizes many types of malignant cells, but does not stain normal cells. Because of the role of Grp94 in the biology of malignant cells, mAb W9 displays anti-tumor activity both in vitro and in vivo.

9:00 Targeting Intracellular Oncoproteins with Immunotherapies

Qi_ZengQi Zeng, Ph.D., Research Director and Professor, Institute of Molecular and Cellular Biology, A*STAR

Traditionally, antibody therapy has been limited to target extracellular oncoproteins, leaving large intracellular oncoproteins untapped. Professor Zeng will discuss a new concept of ‘Targeting Intracellular Oncoproteins with Antibody Therapy or Vaccination’ to vastly widen and usher a new era of cancer immunotherapies. The pioneer research works and views can be found in Cancer Biology & Therapy, 2008; Science Translational Medicine, 2011, Oncotarget, 2012; Cancer Research, 2013; FEBS, 2014.

9:30 Targeting Stress-Inducible Chaperone GRP78 in Cancer

Amy_LeeAmy S. Lee, Ph.D., Professor, Biochemistry & Molecular Biology, Keck School of Medicine of University of Southern California, USC Norris Comprehensive Cancer Center

Glucose Regulated Protein GRP78 (HSPA5) is traditionally regarded as an endoplasmic reticulum chaperone protein critical for protein folding and control of the unfolded protein response. However, a subfraction of GRP78 can relocalize to the cell surface where it exerts regulation on signaling, proliferation, invasion and apoptosis. The preferential expression of GRP78 on the surface of tumor cells but not normal organs in vivo enables antibody-based tumor specific therapy.

10:00 Coffee Break in the Exhibit Hall with Poster Viewing and Poster Awards


FROM THE IMMUNO-ONCOLOGY TRENCHES: Preclinical Monotherapy, Antibody Combination and Bispecific Antibody Approaches

Chairperson’s Remarks

John Haurum, M.D., CEO, F-star GmbH & F-star Biotechnology Ltd.

10:50 Epacadostat (INCB024360): A Novel First-In-Class Inhibitor of IDO1 as Monotherapy and in Combination with other Checkpoint Inhibitors

Peggy Scherle, Ph.D., Vice President, Preclinical Pharmacology, Incyte Corporation

Antibodies to CTLA-4 and PD1/PDL1 have demonstrated unprecedented efficacy in a broad range of tumors types and represent a new paradigm in cancer treatment focused on inhibition of mechanisms that suppress anti-tumoral immunity. Indoleamine-2,3-dioxygenase-1 (IDO1) emerged as an immunotherapy target due to its role in regulating T cell responses. The preclinical characterization and clinical activity of epacadostat, a first-in-class, potent, selective and orally bioavailable small molecule IDO1 inhibitor will be described.

11:20 Glypican-3 as a Liver Cancer Target for Antibody-Based Therapies

Mitchell_HoMitchell Ho, Ph.D., Chief, Antibody Therapy Section, Laboratory of Molecular Biology, NIH NCI

Glypican-3 (GPC3) is expressed in hepatocellular carcinoma. We have developed human monoclonal antibodies that recognize functional sites in GPC3 and inactivate Wnt/Yap signaling pathways known to be important for liver cancer pathogenesis. HN3 is a human heavy-chain antibody that recognizes the core protein of GPC3. The HS20 human antibody recognizes the heparan sulfate chains on glypicans. Furthermore, we found that the HN3-based immunotoxin caused regression of liver cancer in mice. Its mechanism appears to involve both inhibition of cancer signaling (Wnt/Yap) and reduction in protein synthesis. Our recent work establishes GPC3 as a candidate for immunotoxin-based liver cancer therapy.

11:50 Antibodies Targeting Peptide/HLA Complexes for Cancer Therapy

Steffi_UrlingerStefanie Urlinger, Ph.D., Director, R&D, MorphoSys AG

Tumor-specific peptide / HLA complexes make intracellular targets accessible to antibodies. However, the generation of therapeutic antibodies, which recognize a particular peptide / HLA complex specifically, is highly challenging. By identifying and applying appropriate counter-targets we generated fully human, high affinity antibodies against a WT1 peptide / HLA complex. These antibodies bind to target-positive cancer cell lines and outperform similar state-of-the-art antibodies regarding target specificity and binding affinity.

Genentech - small logo12:20 pm Luncheon Presentation: Genentech – Insights into Our Science, People, Postdoc Program & How to Join

Paul Carter, Senior Director, Antibody Engineering, Genentech, Inc.

JT Koerber, Scientist, Antibody Engineering, Genentech, Inc.

Erin Krolikiewicz, Principal Talent Acquisition, Genentech Early Research and Roche Early Research (North America)

Engage with Genentech's world class leaders in Early Research and Development and learn about our unique scientific culture and how to join our team.

1:20 Ice Cream Break in the Exhibit Hall with Poster Viewing

2:00 Chairperson’s Remarks

John Haurum, M.D., CEO, F-star GmbH & F-star Biotechnology Ltd.

2:05 Combination Immunotherapy in Treating Advanced Cancer

Tara_GangadharTara C. Gangadhar, M.D., Assistant Professor, Medicine, Hematology-Oncology Division, Abramson Cancer Center of the University of Pennsylvania

Novel immune therapies have demonstrated increasing efficacy in treating patients with advanced cancer. However, most patients remain resistant to these therapies. An overview of the current strategies to combine immune therapy approaches to improve outcomes and the ongoing research to develop predictive biomarkers of response.

2:35 Rapid Assessment of Bispecific mAb2 Molecules against Immuno-Modulatory Targets

Neil Brewis, Ph.D., Chief Scientific Officer, F-star GmbH & F-star Biotechnology Ltd.

A bottleneck in the discovery of therapeutic bispecific antibodies is the lengthy process of generating stable molecules with sufficient quality and quantity to enable functional assessment and in vivo POC studies. F-star’s proprietary Modular Antibody TechnologyTM addresses this through a robust “plug and play” process allowing the rapid testing of multiple target-specific combinations in vivo. Examples will be provided from the testing of several immuno-oncology products.

3:05 Poster Presentation: A Novel Yeast Display Platform for Fully Human Antibody Discovery
Aizhi Zhao, Department of Immunology, Xijing Hospital, Fourth Military Medical University

3:35 Refreshment Break in the Exhibit Hall with Poster Viewing


ANTIBODIES IN THE CLINIC TO WATCH IN 2016

4:25 Cancer Antibodies to Watch in 2016

Janice_ReichertJanice M. Reichert, Ph.D., Managing Director, Reichert Biotechnology Consulting LLC

The success of novel antibody therapeutics for cancer has made them a primary focus of the biopharmaceutical industry, and antibody-drug conjugates (ADCs) and bispecifics are the most exciting of the antibody formats. This presentation will provide an update on ADCs and bispecifics in clinical development, and, for context, an overview of all antibodies in clinical studies for cancer. Recent approvals and antibodies in regulatory review will also be discussed.


5:25 End of Antibodies for Cancer Therapy

5:30 Registration for Dinner Short Courses*


Recommended Dinner Short Course*

SC11: Clinical Prospects of Cancer Immunotherapy

*Separate registration required.


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