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.

Monday, August 31

IMPROVEMENTS IN TARGETING AND DELIVERY

9:00 am

Chairperson's Opening Remarks

Daniel A. Vallera, PhD, Lion Scholar and Professor; Director, Section on Molecular Cancer Therapeutics; Professor, Therapeutic Radiology, University of Minnesota Masonic Cancer Center
9:05 am

Optimization of Antibody Half-Life for Cancer Therapeutics

Donald J. Buchsbaum, PhD, Professor & Director, Division of Radiation Biology, Department of Radiation Oncology, University of Alabama, 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.

9:25 am

NK Cells as Immune Engagers: A Focus on TriKES

Daniel A. Vallera, PhD, Lion Scholar and Professor; Director, Section on Molecular Cancer Therapeutics; Professor, 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.

Qingcong Lin, PhD, CEO, Biocytogen Boston Corp.

With a robust immune response, RenMab™ Mouse produces fully-human antibodies with high specificity and diverse epitopes. To identify leads, Biocytogen has created a catalog of target-humanized mouse models, allowing to conduct high throughput in vivo hit screening. Lastly, to further select for drug candidates with best clinical translation potential, Biocytogen offers immune-cell humanized mouse models for preclinical pharmacology evaluation. Biocytogen integrates these three mouse models to catalyze the process from target validation to IND application.

10:10 am PANEL DISCUSSION:

What is the Best?

Panel Moderator:
Daniel A. Vallera, PhD, Lion Scholar and Professor; Director, Section on Molecular Cancer Therapeutics; Professor, 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
Panelists:
Donald J. Buchsbaum, PhD, Professor & Director, Division of Radiation Biology, Department of Radiation Oncology, University of Alabama, Birmingham
Qingcong Lin, PhD, CEO, Biocytogen Boston Corp.
10:30 am Coffee Break - View our Virtual Exhibit Hall
12:05 pm Lunch Break - View our Virtual Exhibit Hall

BISPECIFIC ANTIBODIES AND IMMUNOTHERAPY COMBINATIONS

12:40 pm

Chairperson's Remarks

Horacio G Nastri, PhD, Senior Director, Antibody Discovery, Incyte Corporation
12:45 pm

Multispecifics Platform for IO: Challenges and Opportunities

Maria Wendt, PhD, Head, Biologics Research US, Sanofi
1:05 pm

Assessing Immune Oncology Combinations with Common Light Chain Bi-/Tri-Specific Antibodies

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

The Merus Biclonics® and TriclonicsTM platforms utilize proprietary common light chain technologies to rapidly generate panels of multi-specific antibodies. Using unbiased screening approaches, large numbers of multi-specific 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 these platforms in immuno-oncology.

1:50 pm LIVE Q&A:

Session Wrap-Up

Panel Moderator:
Horacio G Nastri, PhD, Senior Director, Antibody Discovery, Incyte Corporation
Panelists:
Maria Wendt, PhD, Head, Biologics Research US, Sanofi
Simon Plyte, PhD, Vice President, Immune Oncology, Merus NV
2:10 pm Refresh Break - View Our Virtual Exhibit Hall
2:30 pm Problem Solving Breakout Discussions - Part A

This session provides the opportunity to discuss a focused topic with peers from around the world in an open, collegial setting. Select from the list of topics available and join the moderated discussion to share ideas, gain insights, establish collaborations or commiserate about persistent challenges.

TABLE 3: What is the Best?

Daniel A. Vallera, PhD, Lion Scholar and Professor; Director, Section on Molecular Cancer Therapeutics; Professor, 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
3:00 pm Refresh Break - View Our Virtual Exhibit Hall
3:20 pm Problem Solving Breakout Discussions - Part B
3:50 pm Refresh Break - View our Virtual Exhibit Hall

PLENARY KEYNOTE SESSION

4:10 pm

Chairperson's Remarks

K. Dane Wittrup, PhD, CP Dubbs Professor, Chemical Engineering & Bioengineering, Massachusetts Institute of Technology
4:15 pm

From Energy to Machine Learning

George M. Church, PhD, Robert Winthrop Professor, Genetics, Harvard Medical School

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 Ph.D. students (Dantas, Raman, Lajoie), 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.

4:40 pm

The Case for Intelligent Design in Protein Engineering

Jamie B. 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.

5:15 pm LIVE Q&A:

Session Wrap-Up

Panel Moderator:
K. Dane Wittrup, PhD, CP Dubbs Professor, Chemical Engineering & Bioengineering, Massachusetts Institute of Technology
Panelists:
George M. Church, PhD, Robert Winthrop Professor, Genetics, Harvard Medical School
Jamie B. Spangler, PhD, Assistant Professor, Biomedical Engineering and Chemical & Biomolecular Engineering, Johns Hopkins University
5:35 pm Happy Hour - View our Virtual Exhibit Hall
6:10 pm Close of Day

Tuesday, September 1

BISPECIFIC ANTIBODIES AND IMMUNOTHERAPY COMBINATIONS (CONT.)

9:20 am

Chairperson's Remarks

Horacio G Nastri, PhD, Senior Director, Antibody Discovery, Incyte Corporation
9:25 am

Combinatorial Approaches to Enhance Bispecific Anti-Tumor Efficacy

Eric Smith, PhD, Senior Director, Bispecifics, Regeneron Pharmaceuticals, Inc.

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.

Larry Green, Ph.D., CEO, Ablexis, LLC

An ADS client project presented the dual challenges of generating low picomolar neutralizing antibodies against a toxic target. ADS overcame these challenges in an exceptionally fast timeline by using Ablexis' AlivaMab Mouse and a novel application of its proprietary AMMPD-DNA immunization coupled with a direct function-first screening paradigm. Together, AlivaMab Mouse and ADS' robust suite of proprietary processes put projects on the fastest and most de-risked path from discovery through development and to market.

 

 

John "Lippy" Lippincott, Ph.D., Vice President of Research, AlivaMab Discovery Services, LLC
10:10 am LIVE Q&A:

Session Wrap-Up

Panel Moderator:
Horacio G Nastri, PhD, Senior Director, Antibody Discovery, Incyte Corporation
Panelists:
Eric Smith, PhD, Senior Director, Bispecifics, Regeneron Pharmaceuticals, Inc.
Larry Green, Ph.D., CEO, Ablexis, LLC
John "Lippy" Lippincott, Ph.D., Vice President of Research, AlivaMab Discovery Services, LLC
10:30 am Coffee Break - View our Virtual Exhibit Hall

TARGETING B7-H3: BRINGING IT FORWARD TO CLINICAL APPLICATION

10:40 am

Chairperson's Remarks

Soldano Ferrone, PhD, Professor-in-Residence, Surgery, Massachusetts General Hospital
10:45 am

Targeting B7-H3 with Multiple Therapeutic Modalities

Ezio Bonvini - 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), CD3 bispecific DART® molecule (MGD009) and ADC (MGC018) to target NK cells, T cells, or direct a cytotoxic payload to B7-H3. The strategic rationale and development update will be presented.


11:05 am

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

Soldano Ferrone, PhD, Professor-in-Residence, 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 recover “exhausted” T cells will be shown to enhance the antitumor activity of antibody-based strategies which target B7-H3.

Ernest Smith, 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.

11:55 am LIVE Q&A:

Session Wrap-Up

Panel Moderator:
Soldano Ferrone, PhD, Professor-in-Residence, Surgery, Massachusetts General Hospital
Panelists:
Ezio Bonvini - MacroGenics, Inc.
Ernest Smith, Senior Vice President, Research & CSO, Vaccinex, Inc.
12:15 pm Lunch Break - View Our Virtual Exhibit Hall

EMERGING TARGETS

12:45 pm

Chairperson's Remarks

Mitchell Ho, PhD, Chief, Antibody Therapy Section, Laboratory of Molecular Biology, National Cancer Institute, NIH
12:50 pm

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

Nina Shah, Associate Professor, Medicine, University of California, San Francisco

Chimeric antigen receptor (CAR) T cells have given new hope to patients with multiple myeloma. In this session, we will review the rationale behind BCMA-CAR T therapy.  We will also review clinical data on efficacy and toxicity. Finally, we will discuss the unmet needs in this space. We will explore new avenues, including cell culture, cell engineering and patient selection, being explored to enhance the success of this promising therapy.

1:10 pm

CAR T Cells Targeting CD123 or Other Targets

M. Eric Kohler, PhD, Instructor, Blood & Marrow Transplant & Cellular Therapeutics, Children's Hospital 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. Approaches to reduce the emergence of resistant leukemia associated with CAR T cell therapy for leukemia will be discussed.

1:30 pm

Session Wrap-Up

Panel Moderator:
Mitchell Ho, PhD, Chief, Antibody Therapy Section, Laboratory of Molecular Biology, National Cancer Institute, NIH
Panelists:
Nina Shah, Associate Professor, Medicine, University of California, San Francisco
M. Eric Kohler, PhD, Instructor, Blood & Marrow Transplant & Cellular Therapeutics, Children's Hospital Colorado
2:25 pm Refresh Break - View our Virtual Exhibit Hall

EMERGING TARGETS (CONT.)

2:30 pm

Chairperson's Remarks

Mitchell Ho, PhD, Chief, Antibody Therapy Section, Laboratory of Molecular Biology, National Cancer Institute, NIH
2:35 pm

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

David J. 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.

2:50 pm

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

Mitchell 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.

3:10 pm

Session Wrap-Up

Panel Moderator:
Mitchell Ho, PhD, Chief, Antibody Therapy Section, Laboratory of Molecular Biology, National Cancer Institute, NIH
Panelists:
David J. FitzGerald, PhD, Chief, Biotherapy Section, Laboratory of Molecular Biology, CCR, National Cancer Institute, NIH
3:40 pm Close of Antibodies for Cancer Therapy





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