Antibodies for Cancer Therapy


Antibodies have become the most sought-after tools in drug discovery, with bispecific antibodies and cell engagers leading the pack of new constructs. New insights on the tumor microenvironment and the microbiome can determine how successful a therapeutic strategy will be, and new imaging tools will help improve delivery of antibody drugs. The 10th Annual Antibodies for Cancer Therapy conference at PEGS will assemble an all-star roster of speakers to explore current results and learn best practices for moving molecules into the clinic.

Final Agenda

Scientific Advisory Board

Soldano Ferrone, MD, PhD, Division of Surgical Oncology, Surgery, Massachusetts General Hospital
Mitchell Ho, PhD, Chief, Antibody Therapy Section, Laboratory of Molecular Biology, National Cancer Institute, NIH
Horacio G. Nastri, PhD, Senior Director, Antibody Biotherapeutics, Incyte Corporation
Daniel A. Vallera, PhD, Lion Scholar and Professor, Director, Section on Molecular Cancer Therapeutics; Professor of Therapeutic Radiology, University of Minnesota Masonic Cancer Center

SUNDAY, MAY 3

Recommended Short Course(s)*

SC1: Clinical Assessment of Immunogenicity of New Modalities: Focus on Bispecific Antibodies, Gene Therapy and Oligonucleotides

SC8: Engineering Better Antibody Therapeutics Using Computational Approaches

*Separate registration required.

MONDAY, MAY 4

7:00 am Registration and Morning Coffee

IMPROVEMENTS IN TARGETING AND DELIVERY

8:30 Chairperson’s Opening Remarks

Daniel Vallera, PhD, Lion Scholar and Professor; Director, Section on Molecular Cancer Therapeutics; Professor of Therapeutic Radiology, University of Minnesota Masonic Cancer Center

8:40 Discovery and Clinical Translation of ONC201/TIC10

El-Deiry_WafikWafik El-Deiry, MD, PhD, FACP, Associate Dean for Oncologic Sciences, Warren Alpert Medical School, Brown University

The presentation will review the discovery of ONC201/TIC10 as a TRAIL pathway-inducing drug that has entered clinical trials for multiple tumor types. The story includes efforts to unravel cell death induced by chemotherapy and the tumor suppressor p53 that led to discovery of TRAIL death receptor DR5. We explored combinatorial therapeutics with TRAIL as well as mechanisms of cell death and drug resistance. ONC201/TIC10 emerged from a cell-based phenotypic screen seeking small molecules that upregulate the TRAIL gene promoter independent of p53. Initial findings included inhibitory effects of ONC201/TIC10 on Akt and ERK leading to nuclear localization of Foxo3a and transcriptional upregulation of TRAIL. Our subsequent studies unraveled upregulation of an integrated stress response in tumor cells treated with ONC201 as well as effects targeting cancer stem cells. The first-in-human study reported by Stein et al., Clinical Cancer Research, 2017, showed the orally bioavailable drug was well tolerated and has an efficacy signal in several tumor types, including prostate cancer and endometrial cancer, among others. ONC201 has activity against the diffuse intrinsic pontine glioma (DIPG) that has the H3 K27M mutation. Our current efforts are focused on mechanisms of action including the role of dopamine receptors and ClpP, mechanisms of resistance, combinatorial therapeutics, and analysis of promising ONC201 analogues. The work involves basic science discovery to clinical impact.

9:10 Optimization of Antibody Half-Life for Cancer Therapeutics

Buchsbaum_DonaldDonald Buchsbaum, PhD, Professor and Director, Division of Radiation Biology, Department of Radiation Oncology, University of Alabama at Birmingham

There are many approaches to the use of monoclonal antibodies in cancer therapy. A factor associated with efficacy and toxicity is the circulation half-life, which relates to antibody size (intact vs. fragments), glycosylation, humanization, pegylation, albumin binding, coupling to nanoparticles, and use of a masking domain to protect the antibody from an antigen sink. Half-life is important for direct antibody therapeutics and cytotoxic antibody conjugates. Examples will be discussed.

9:40 Selecting the Best Tumor Targets for Imaging

Sier_CornelisCornelis Sier, PhD, Molecular Biologist, Project Leader Targeting, Department of Image-Guided Oncologic Surgery, Leiden University Medical Center

Tumors are targeted with a wide range of monoclonal antibodies, ligand-based proteins, peptides, RNAs, and small molecules. The majority of these compounds are directed against cell membrane-associated proteins. The function and other biological characteristics of these proteins determine their location, availability and distribution on the cell membrane, making them more (or less) accessible for tracers. In this presentation, we evaluate the characteristics of the major cancer-associated membrane proteins and discuss their overall usability for cancer targeting.

10:10 Networking Coffee Break

10:50 Review of Targets and Drug Development Evolution

Frankel_ArthurArthur Frankel, MD, Chief, Hematology/Oncology, Mitchell Cancer Institute, University of South Alabama

Elzonris or tagraxofusp-erzs is a fusion protein composed of the catalytic and translocation domains of diphtheria toxin fused via a Met-His linker to human IL3. It was initially developed for targeting stem cells in AML. The Phase I/II study in this indication showed a low response rate likely due to variable expression of high affinity IL3R (CD123 plus CDw131). High affinity IL3R are needed for internalization, translocation and protein synthesis inactivation. The agent was then explored in other diseases dependent on IL3R signaling. Dramatic response rates were observed in blastic plasmacytoid dendritic cell neoplasm (BPDCN) and FDA approval was obtained for this condition both in adults and children >2 years old. Current clinical trials in other IL3R-rich malignancies including CMML, MF, subsets of AML, CML, MF, MDS, NHL, MM, HCL, ALL, and the autoimmune disorder with abnormal IL3R-positive cells – systemic sclerosis – are ongoing. Further, increased malignant cell synthesis of the diphthamide amino acid (the diphtheria toxin catalytic target) with HDAC inhibitors is being tested to overcome Elzonris resistance. Thus, careful investigations of the target and its physiology expands the clinical usefulness of this compound.

11:20 NK Cells as Immune Engagers: A Focus on TriKES

Vallera_DanielDaniel Vallera, PhD, Lion Scholar and Professor; Director, Section on Molecular Cancer Therapeutics; Professor of Therapeutic Radiology, University of Minnesota Masonic Cancer Center

TriKEs are trispecific natural killer (NK) cell engagers and novel immunotherapeutic drugs consisting of two antibody scFV fragments; one recognizing NK cells, the other, tumor markers, both cross-linked with cytokine IL-15. The talk will focus on improvements to the platform made using camelid technology, clinical progress against liquid tumors, prospects for solid tumor trials, and prospects for adverse reactions. We will discuss xenograft studies and their relevancy to clinical translation.

11:50 PANEL DISCUSSION: What is the Best?

Vallera_DanielModerator: Daniel Vallera, PhD, Lion Scholar and Professor; Director, Section on Molecular Cancer Therapeutics; Professor of Therapeutic Radiology, University of Minnesota Masonic Cancer Center


Panelists:

El-Deiry_WafikWafik El-Deiry, MD, PhD, FACP, Associate Dean for Oncologic Sciences, Warren Alpert Medical School, Brown University


Buchsbaum_DonaldDonald Buchsbaum, PhD, Professor and Director, Division of Radiation Biology, Department of Radiation Oncology, University of Alabama at Birmingham


Sier_CornelisCornelis Sier, PhD, Molecular Biologist, Project Leader Targeting, Department of Image-Guided Oncologic Surgery, Leiden University Medical Center


Frankel_ArthurArthur Frankel, MD, Chief, Hematology/Oncology, Mitchell Cancer Institute, University of South Alabama


  • Best target for solid tumors
  • Best route of delivery
  • Best way of minimizing adverse reactions
  • Best way of prolonging half-life of therapeutics
  • 12:20 pm Novel Cell-Based Assays to Enable Immunotherapy Drug Development for Checkpoint Receptors

    Lin-Jones_JenniferJennifer Lin-Jones, Senior Group Leader, Assay Development, Research & Development, Eurofins DiscoverX

    Checkpoint receptors are established therapeutic targets for many cancers. Cell-based assays are necessary to screen for such drugs, but their development is challenging due to primary cells and long protocols. On that front, we present data for PathHunter Checkpoint assays for immunotherapy targets like PD-1 and SIRPα. These assays are biologically relevant and use simple, homogenous protocols yielding results in 24 hours. Demonstrating excellent robustness and reproducibility, they are successfully used in potency testing and lot release.

    12:50 Session Break

    12:55 Luncheon Presentation I to be Announced

    1:25 Luncheon Presentation II (Sponsorship Opportunity Available)

    1:55 Session Break

    2:20 Problem-Solving Breakout Discussions - View All Breakout Discussion Topics

    TABLE: What is the Best?

    Moderator: Daniel Vallera, PhD, Lion Scholar and Professor; Director, Section on Molecular Cancer Therapeutics; Professor of Therapeutic Radiology, University of Minnesota Masonic Cancer Center

    • Best target for solid tumors
    • Best route of delivery
    • Best way of minimizing adverse reactions
    • Best way of prolonging half-life of therapeutics

    3:20 Networking Refreshment Break

    PLENARY KEYNOTE SESSION

    4:00 Chairperson’s Remarks

    K. Dane Wittrup, PhD, J.R. Mares Professor, Chemical Engineering & Bioengineering, Massachusetts Institute of Technology

    4:10 From Energy to Machine Learning

    George-ChurchGeorge Church, PhD, Professor of Genetics, Harvard Medical School; Professor of Health Sciences and Technology, Harvard and the Massachusetts Institute of Technology (MIT)

    In 1974, I adapted energy optimization methods for use in models of nucleic acids, protein and their interactions, and then for use in crystallographic refinement. In the last days of the second millennium, David Baker's team won the Critical Assessment of Structure Prediction (CASP) by an unbelievable margin. Since then, our labs exchanged 3 PhD students (Dantas, Raman, Lajoie), for Wannier from Mayo's group, Stranges from Kuhlman, and Mandell from Kortemme. We engineered new sensor proteins for metabolic engineering, essential proteins with non-standard amino acids for biocontainment, and polymerase-pore fusions for nanopore sequencing. None of this prepared us for the revolution following Gleb Kuznetsov joining our lab in 2012, joined soon by Surge Biswas, Pierce Ogden, Ethan Alley, and Sam Sinai. Together we abruptly moved to "sequence only" deep machine learning for protein design – ranging from fluorescent proteins to AAV capsids to antibodies. When combined with libraries of millions of designed gene segments from chip-synthesis and rapid testing, each design cycle can take large leaps in sequence space and function space.

    4:55 The Case for Intelligent Design in Protein Engineering

    spangler-jaimeJamie Spangler, PhD, Assistant Professor, Biomedical Engineering and Chemical & Biomolecular Engineering, Johns Hopkins University

    Directed evolution is in its prime, and it is deepening our understanding of biological systems and empowering therapeutic design. Recent breakthroughs in structural biology, computational design, and high-dimensional data analytics afford us the unprecedented opportunity to apply molecular, structural, and computational principles to guide protein engineering, employing a so-called “intelligent design” approach. This talk will highlight how my lab harnesses this interfacial approach to overcome the deficiencies of natural proteins.

    5:40 Welcome Reception in the Exhibit Hall with Poster Viewing (Co-Sponsorship Opportunity Available)

    7:15 End of Day

    TUESDAY, MAY 5

    8:00 am Registration and Morning Coffee

    BISPECIFIC ANTIBODIES AND IMMUNOTHERAPY COMBINATIONS

    8:25 Chairperson’s Remarks

    Horacio Nastri, PhD, Senior Director, Antibody Biotherapeutics, Incyte Corporation


    8:30 KEYNOTE PRESENTATION: Redirecting T Cells for Cancer Immunotherapy Using Next-Generation Bispecific Antibodies and Fusion Proteins

    Umana_PabloPablo Umaña, PhD, Head, Cancer Immunotherapy Discovery, Roche Innovation Center Zurich (Roche Glycart AG)

    This talk will discuss a new generation of therapeutic approaches to redirect and enhance T cells attacks on cancer cells. The approaches are based on combinations of systemically administered, recombinant proteins that have been engineered to enhance their activity for stimulating T cells in tumors and/or lymph nodes vs. normal tissues.

    9:00 FEATURED PRESENTATION: Bispecifics and Beyond: Approaches for Identification of Effective Cancer Therapeutics

    Nixon_AndrewAndrew Nixon, PhD, Vice President, Biotherapeutics Molecule Discovery, Boehringer Ingelheim


    9:30 Assessing Immune Oncology Combinations with Common Light Chain Bispecific Antibodies

    Plyte_SimonSimon Plyte, PhD, Vice President, Immune Oncology, Merus NV

    The Merus Biclonic® platform utilizes proprietary common light chain technology to rapidly generate panels of bispecific antibodies. Using unbiased screening approaches large numbers of bispecific antibodies can be tested in relevant biological assays to identify those with the strongest or even new biological responses. Case studies will be presented demonstrating the application of the Merus Biclonic platform in immuno-oncology.

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

    10:50 BiSAb T Cell Engagers that Target Tumor-Specific pMHC Antigens for Solid Tumors

    Rainey_JonahG. Jonah Rainey, PhD, Vice President, Antibody Therapeutics, Gritstone Oncology

    Bispecific antibody T cell engagers have shown great promise in hematologic malignancies. However, their application to solid tumors has been limited due to the paucity of highly tumor-specific targets. Here we present validated targets predicted by our EDGE (Epitope Discovery in cancer GEnomes) artificial intelligence platform for pMHC, generation of antibody leads, and optimization of a drug candidate as a BiSAb T cell engager.

    11:20 Combinatorial Approaches to Enhance Bispecific Anti-Tumor Efficacy

    Smith_EricEric Smith, PhD, Senior Director, Bispecifics, Regeneron Pharmaceuticals

    This presentation will describe Regeneron’s bispecific platform and present preclinical data on REGN4018, a clinical-stage T cell engaging bispecific-targeting Muc16 for solid tumor indications. In addition, status updates on Regeneron’s other clinical-stage bispecific antibodies (REGN1979, REGN5458, REGN5678) will be presented as well as a discussion of new combinatorial approaches being taken to enhance bispecific anti-tumor efficacy.

    TARGETING B7-H3: BRINGING IT FORWARD TO CLINICAL APPLICATION

    Chairperson’s Remarks

    Soldano Ferrone, MD, PhD, Division of Surgical Oncology, Surgery, Massachusetts General Hospital

    11:50 Targeting B7-H3 with Multiple Therapeutic Modalities

    Ezio Bonvini, MD, CSO, MacroGenics, Inc.

    B7-H3 expression has been associated with cancer progression and poor prognosis. While its immunological function is unclear, B7-H3 remains an attractive target for tumor-directed interventions, owing to its broad cancer-associated overexpression. We have developed an Fc-enhanced mAb (enoblituzumab), a CD3 bispecific DART® molecule (MGD009) and an ADC (MGC018) to target NK cells, T cells or direct a cytotoxic payload to B7-H3. The strategic rationale and a development update will be presented.

    12:20 pm Session Break

    12:25 Luncheon Presentation I to be Announced


    12:55 LUNCHEON PRESENTATION II: Use of Mammalian Virus Display to Select Antibodies Specific for Complex Membrane Antigens

    Ernest Smith, PhD, Senior Vice President, Research, CSO, Vaccinex, Inc.

    We have developed a technology to enable direct incorporation of multipass membrane proteins such as GPCRs and ion channels into the membrane of a mammalian virus. Antigen-expressing virus can be readily purified and used for antibody selection using either vaccinia, phage or yeast display methods. This method is rapid, does not require any detergents or refolding, and can be applied to multiple cell types in order to provide properly folded protein.

    1:25 Ice Cream Break in the Exhibit Hall with Poster Viewing and Poster Award

    TARGETING B7-H3: BRINGING IT FORWARD TO CLINICAL APPLICATION (CONT.)

    2:00 B7-H3 Targeted Antibody-Based Combinatorial Immunotherapy for the Treatment of Solid Tumors

    Ferrone_SoldanoSoldano Ferrone, MD, PhD, Division of Surgical Oncology, Surgery, Massachusetts General Hospital

    B7-H3, a Type I transmembrane, is a member of the B7 superfamily of ligands. It is an attractive target of antibody-based immunotherapy of solid tumors, since i.) it is highly expressed on malignant cells with limited heterogeneity, ii.) it is expressed not only on differentiated cancer cells, but also on cells which display the phenotypic and functional characteristics of cancer initiating cells, and iii.) has a restricted distribution in normal tissues. Strategies will be described to eliminate both differentiated cancer cells and cancer initiating cells, utilizing both our B7-H3-specific mAb 376.96 and Fc receptors. In addition, approaches which upregulate B7-H3 expression on tumor cells and which recover “exhausted” T cells will be shown to enhance the antitumor activity of antibody-based strategies which target B7-H3.

    EMERGING TARGETS

    2:30 Chairperson’s Remarks

    Mitchell Ho, PhD, Chief, Antibody Therapy Section, Laboratory of Molecular Biology, National Cancer Institute, NIH

    2:35 BCMA-Directed CAR T Cells for Myeloma: What Have We Learned?

    Cohen_AdamAdam Cohen, MD, Assistant Professor, Hematology & Oncology, Perelman Center for Advanced Medicine, University of Pennsylvania

    B-cell maturation antigen (BCMA) is a cell surface receptor expressed on both normal and malignant plasma cells and is emerging as a promising new target in myeloma therapy. Initial studies of BCMA-specific CAR T cells have demonstrated unprecedented response rates in highly refractory patients. Toxicities include cytokine release syndrome and neurotoxicity, without unexpected “off-tumor” effects. The durability of remissions has been more variable, and current strategies seeking to understand and overcome mechanisms of resistance and improve outcomes will be discussed.

    Trianni 3:05 Presentation to be Announced

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

    4:25 CAR T Cells Targeting CD123 or Other Targets

    Fry_TerryTerry Fry, MD, Professor of Pediatrics, Hematology and Immunology, University of Colorado

    Relapse after lineage-targeted immunotherapy for B cell leukemia associated with antigen loss is a relatively frequent occurrence. Phenotypic heterogeneity in AML suggests that this may also emerge as a pattern following targeted immunotherapy for this disease as well. Approaches to reduce the emergence of resistant leukemia associated with CAR T cell therapy for leukemia will be discussed.

    4:55 Development of Cancer-Reactive Antibodies Focused to the 287-302 Amino Acid Loop of the Human Epidermal Growth Factor Receptor

    Fitzgerald_DavidDavid FitzGerald, PhD, Chief, Biotherapy Section, Laboratory of Molecular Biology, CCR, National Cancer Institute, NIH

    The 287-302 loop from EGFR is exposed on EGFRvIII (deletion of exons 2-7), partially exposed on some cancers but cryptic on cells expressing WT EGFR. Seven antibodies to this loop reacted with EGFRvIII but not EGFR WT. One antibody, 40H3, also exhibited binding to MDA-468 and A431 cells but not to non-cancerous WI-38 cells. The 40H3 antibody was engineered as a potent recombinant immunotoxin for treating tumors with abnormal EGFR.

    5:25 Glypicans as Emerging CAR T Cell Therapy Targets: GPC3 and Beyond

    Ho_MitchellMitchell Ho, PhD, Chief, Antibody Therapy Section, Laboratory of Molecular Biology, National Cancer Institute, NIH

    For the past ten years, we have studied the role of GPC3 in regulating Wnt signaling and developed antibody therapeutics including CAR T cells, antibody-drug conjugates and immunotoxins for treating liver cancer. In recent years, we applied what we learned from GPC3 biology to explore the roles of other glypicans in solid tumors and established GPC2 and GPC1 as new targets of CAR T cell therapy for neuroblastoma and pancreatic cancer, respectively.

    5:55 End of Antibodies for Cancer Therapy

    5:30 Registration for Dinner Short Courses


    6:00-8:30 pm Recommended Dinner Short Course*

    SC10: CAR T Cell Therapy from A-Z

    *Separate registration required.

    * The program is subject to change without notice, due to unforeseen reason.

    Choose your language
    Japanese
    Traditional Chinese
    Simplified Chinese
    Korean


    Update History
    2020/03/04
    Agenda,Sponsor updated
    2020/02/13
    Agenda,Speaker,Sponsor updated
    2020/01/08
    Agenda,Sponsor updated
    2019/12/09
    Event Information updated
    2019/11/25
    Sponsor updated



    View By: