The specificity of antibodies makes them an ideal weapon against cancer. Novel antibody constructs are advancing rapidly through discovery to preclinical and clinical development with greater selectivity for specific cell populations and potency.
The Eighth Annual Antibodies for Cancer Therapy meeting has become a pivotal forum for reviewing the newest trends in design of novel constructs, emerging target investigation, preclinical and clinical data assessment and latest approaches for
selective targeting.
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
Final
Agenda
Sunday, April 29
SC2: Translational Considerations for Development of Monoclonal Antibodies and Emerging Constructs: Part I: Focus on Construct Design
SC7: Translational Considerations for Development of Monoclonal Antibodies and Emerging Constructs: Part 2: Focus on Preclinical Development
*Separate registration required.
MONDAY, APRIL 30
7:00 am Registration (Commonwealth Hall) and Morning Coffee (Harbor Level)
8:30 Chairperson’s Remarks
Mitchell Ho, PhD, Senior Investigator, National Cancer Institute, NIH
8:40 Immunotherapy for Liver Cancer: How and Targeting What?
Tim F. Greten, MD, Senior Investigator, GI Maligancy Section, Thoracic and GI Oncology Branch, Center for Cancer Research,
National Cancer Institute
Hepatocellular carcinoma (HCC) is the sixth most frequent neoplasm and the second leading cause of cancer-related deaths worldwide. HCC typically arises in the context of liver cirrhosis caused by viral infection, environmental factors, toxins,
and in rare cases genetic conditions. We have been studying how the tumor microenvironment affects anti-tumor immunity and study novel immune based treatment approaches for the treatment of patients with liver cancer.
9:10 Improving Cancer Therapy through Simultaneous Ablation of CD276/B7-H3-Positive Tumor Cells and Tumor Vasculature
Bradley St. Croix, PhD, Senior Associate Scientist, Head, Tumor Angiogenesis Unit, Mouse Cancer Genetics Program,
National Cancer Institute
CD276 is frequently overexpressed in tumors on both tumor cells and tumor infiltrating blood vessels that fuel its growth, making it an alluring dual compartment target for an ADC therapy. The development of anti-CD276 ADCs armed with MMAE or
PBD will be discussed, along with the mechanistic basis for the differential efficacy of these agents against tumor-associated stroma and implications for development of other vascular-targeted ADCs.
9:40 Pharmacological Characterization of Anti-Glypican 3/CD3 Bispecific T Cell-Redirecting Antibody ERY974
Junichi Nezu, PhD, Senior Specialist, Project & Lifecycle Management Unit, Chugai Pharmaceutical, Co., Ltd.
The bispecific T cell redirecting antibody (TRAB) is a new form of promising immunotherapy. We generated a novel TRAB, ERY974, targeting tumor-specific antigen Glypican-3 (GPC3). Using a mouse model reconstituted with human immune cells, we revealed
that ERY974 is highly effective in killing various tumor types including those with non-immunogenic features. In the presentation, combination effect of ERY974 with other anti-cancer agents and its possible mechanism will also be discussed.
10:10 Networking Coffee Break (Harbor & Mezzanine Level)
10:45 Chairperson’s Remarks
Soldano Ferrone, MD, PhD, Surgical Oncology, Surgery, Massachusetts General Hospital
William R. Strohl, PhD, Owner and President, BiStro Biotech Consulting, LLC
New technologies, including multitargeted bispecific antibodies, T cell redirecting bispecific antibodies, engagement of T cell checkpoint targets, and autologous and allogeneic forms of chimeric-antigen receptor (CAR) T and NK cells, have
been employed over the past several years to improve the odds of treating cancer successfully. This presentation will explore the current clinical use of these technologies and will highlight promising new advances that offer hope for
future cancer therapy.
11:20 Targeting Netrin-1: From Modulating Cancer Plasticity to Strengthening Immunotherapy
Patrick Mehlen, PhD, CEO Netris Pharma, Centre Léon Bérard
Netrin-1, a secreted cue, has been shown to be up-regulated in a large fraction of human cancers and has been show to promote tumor progression. An anti-netrin-1 mAb called NP137 has been preclinically developed and is currently assessed in
a first-in-man-first-in-class Phase I clinical trial. The NP137 shows preclinical efficacy related to a specific effect on cancer plasticity, and preclinical data support the importance of combining NP137 with immune-checkpoint inhibitors.
We will present preclinical and preliminary clinical data.
11:50 Antibody Protein Sequencing with Mass Spectrometry
Mingjie Xie, CEO, Rapid Novor, Inc.
Many applications in antibody engineering require the direct sequencing of antibody proteins. At Rapid Novor (rapidnovor.com), we have developed a robust workflow and routinely sequenced antibody proteins. Here we share the success experiences,
examine common mistakes novices make, and present our practices to ensure the correctness of every amino acid.
12:20 pm Streamlined Discovery and Production of Antibodies
Sirle Saul, Key Account and Technology Officer, Business Development, Icosagen Technologies, Inc.
Target selection is followed by development and production of monoclonal antibodies. HybriFree technology enables to discover recombinant antibodies by direct cloning from B-cells of immunized rabbits, chicken or from hybridomas. The subsequent
production in mammalian cell factories can be done using QMCF technology. This scalable episomal expression system enables to produce up to gram quantities of recombinant antibodies (including non-fucosylated) with low endotoxin levels
in few weeks and generate production cell banks in 10 days.
Sirle Saul, Key Account and Technology Officer, Business Development, Icosagen Technologies, Inc.
12:50 Luncheon Presentation I: In Vivo Platform for Generating Human “Heavy Chain Only” Antibodies for Drug Discovery
Frank Grosveld, PhD, Professor, Cell Biology, Erasmus MC; Founder, Harbour Antibodies BV, Harbour BioMed
The majority of currently approved fully human antibody drugs are generated in vivo from transgenic animal platforms. Here we present recent development from Harbour Antibodies utilizing transgenic mice to generate novel “heavy chain
only” antibodies (HCAb). The Harbour HCAb platform enables the development of antibody fragment-based therapeutics such as nanobodies, bi-specific or multivalent antibodies and CAR-T with favorable drug-like properties.
1:20 Luncheon Presentation II (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:50 Session Break
2:20 Problem-Solving Breakout Discussions (Commonwealth Hall)
Bispecific Antibodies – Beyond T Cell Recruitment
Mark Throsby, PhD, CSO, Merus NV
- Can the T cell recruitment approach work outside hematological cancers?
- How to select target combinations for bispecific approaches?
- Design or screen?
- What is going to be the best format?
Bispecific Antibodies – What is The Best Partner for Anti-PD1/PDL1?
Moderator: Tim F. Greten, MD, Senior Investigator, GI Maligancy Section, Thoracic and GI Oncology Branch, Center for Cancer Research, National Cancer Institute
- TGF-beta trap
- Advantage of bispecific antibodies over combination therapies
- What are the best indications?
3:20 Networking Refreshment Break (Harbor & Mezzanine Level)
4:00 Chairperson’s Remarks
Peter Fung, PhD, Senior Manager Product Marketing, NanoTemper Technologies
4:10 Challenges and Opportunities in Engineering Protein Biopharmaceuticals
K. Dane Wittrup, PhD, C.P. Dubbs Professor, Chemical Engineering and Biological Engineering; Associate Director, Koch Institute
for Integrative Cancer Research, Massachusetts Institute of Technology (MIT)
Arthur C. Clarke’s First Law posits that “When a distinguished but elderly scientist states that something is possible, he is almost certainly right. When he states that something is impossible, he is very probably wrong.”
Bearing this in mind, in this talk, I will highlight areas of protein drug development that appear poised for breakthroughs in the coming decade or so.
4:55 The Next Generation of Cancer Immunotherapy: Targeting Myeloid Immune Checkpoints
Kipp Weiskopf, MD, PhD, Resident Physician, Internal Medicine, Brigham and Women’s Hospital
Immune cells of the myeloid lineage hold tremendous potential as effectors of cancer immunotherapy. The CD47/SIRPα axis is a key molecular pathway that governs the interaction between myeloid cells and tumors. Therapies that target the
interaction are effective across multiple preclinical models of cancer and are now under investigation in clinical trials. Further studies have revealed additional regulators of myeloid cell activation that can be exploited as myeloid
immune checkpoints.
5:40 Welcome Reception in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
7:15 End of Day
TUESDAY, MAY 1
8:00 am Registration (Commonwealth Hall) and Morning Coffee (Harbor Level)
8:25 Chairperson’s Remarks
Soldano Ferrone, MD, PhD, Surgical Oncology, Surgery, Massachusetts General Hospital
8:30 CAR T Cells Targeting B7-H3
Gianpietro Dotti, MD, Lineberger Comprehensive Cancer Center Member, Professor, Microbiology and
Immunology; Director, Lineberger Immunotherapy Program, University of North Carolina School of Medicine
The field of chimeric antigen receptors (CARs) in hematologic malignancies has been largely dominated by the adoptive transfer of T cells expressing the CD19-specific CAR for therapy of acute lymphoid leukemia and non-Hodgkin’s lymphomas.
We generated CAR Ts targeting the B7-H3 antigen that is expressed by many solid tumors. B7-H3.CAR Ts effectively eliminate several solid tumor cells in vitro, in PDAC orthotopic and metastatic xenograft
NSG mouse models, and patient-derived xenograft (PDX) orthotopic NSG mouse models. B-H3.CAR Ts recognize the murine B7-H3, but we did not observe any decrease in hematopoietic cell numbers in blood, spleen or bone marrow, or significant
tissue damage, which further encourage the clinical translation.
9:00 Targeting B7-H3 with Multiple Approaches
Ezio Bonvini, MD, Senior Vice President, Research & CSO, MacroGenics, Inc.
B7-H3 is a member of the B7-family of immune regulators. While its immunological role remains unknown, B7-H3 expression is a negative prognostic factor in cancer and, owing to its limited expression in normal tissues, a suitable tumor
target for exploitation by a variety of mechanistic interventions.
9:30 B7-H3 is a Potential Antibody Drug Conjugate Target for the Treatment of Solid Tumours
Kelli Ryan, PhD, Senior Scientist, Oncology Department, MedImmune
B7H3 is a member of the B7 family of TCR modulatory proteins that is also significantly expressed on the surface of tumor cells and the tumor vasculature, and can be a poor prognostic marker for certain cancers. This presentation will
summarize the preclinical data generated upon evaluating ADCs targeting B7H3 with either tubulysin or PBD payloads.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
Chairperson’s Remarks
Horacio G. Nastri, PhD, Senior Director, Antibody Biotherapeutics, Incyte Corporation
10:50 Overcoming Resistance to HER2-Targeted Therapy with a Novel HER2/CD3 Bispecific Antibody
Nai-Kong V. Cheung, MD, PhD, Head, Neuroblastoma Program; Enid A. Haupt Endowed Chair, Pediatric
Oncology, Memorial Sloan Kettering Cancer Center
HER2 is an established tumor target for breast, ovarian and gastric cancers. We explored a novel HER2/CD3 bispecific antibody (HER2-BsAb) platform which, in addition to preserving the anti-proliferative effects of trastuzumab, recruits
and activates circulating T cells, promoting T cell tumor infiltration, as well as ablating HER2(+) tumors resistant to standard HER2-targeted therapies. HER2-BsAb-mediated cytotoxicity is relatively insensitive to PD-1/PD-L1 immune
checkpoint inhibition, although the addition of ICI does improve its efficacy.
11:20 Unbiased Functional Screening of Large Bispecific Antibody Panels to Unlock Novel Biology
Mark Throsby, PhD, CSO, Merus NV
The bispecific antibody format represents an emerging therapeutic modality. We have developed a set of robust and validated technologies that permits unbiased in-format functional screening to identify human full-length IgG bispecific
antibodies candidates with superior therapeutic properties. Two case studies will be presented where this approach has been successfully employed to discover lead candidates with differentiating properties that are now in clinical
development.
11:50 Balancing Selectivity and Efficacy of Bispecific EGFR x c-MET Antibodies and Antibody-Drug Conjugates
Achim Doerner, PhD, Principal Scientist, Protein Engineering and Antibody Technologies, Merck KGaA Darmstadt, Germany
Therapies targeting EGFR often suffer from toxicities due to basal EGFR expression in normal tissue and may face limited efficacy through c-MET activation. Hence, we aim to construct bispecific EGFR x c-MET antibodies employing affinity-optimized
binding moieties to balance both high selectivity and anti-tumor efficacy and to evaluate their potential for an innovative antibody-drug conjugate approach.
12:20
pm Luncheon Presentation I: OmniAb Engineered Animals for the Discovery of Fully Human Antibodies
Bill Harriman, PhD, MBA, Vice President, Antibody Discovery Services, Ligand
OmniRat®, OmniFlic®, OmniMouse® and OmniChicken™ use newly patented technology and deliver fully human OmniAb antibodies with high affinity, specificity, expression, solubility and stability. While transgenic mice expressing
human antibodies date back to the 1990's, in recent years OMT and Crystal scientists were the first to create rats and chickens expressing diversified repertoires of antibodies with fully human idiotypes. OmniMouse® complements
that to form the industry's only platform with three species.
12:50
Luncheon Presentation II: Novel Method for Generation of Anti Idiotype Antibodies for PK Assay
Saurabh Joshi, Senior Lead Investigator, Oncology, Syngene International Limited
Generation of anti idiotype (anti ID) antibodies is a must for any biotherapeutic antibody program. This critical reagent generation is a strict time bound requirement. Identification of blocking as well as non-blocking anti IDs can become
challenging task by simply immunizing biotherapeutic antibody molecule in the animals. This traditional approach is time consuming and laborious. Here, we have developed a novel immunization platform which provide increased chances
of identifying anti IDs with less screening.
1:20 Ice Cream Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
Chairperson's Remarks
Mitchell Ho, PhD, Chief, Antibody Therapy Section, Laboratory of Molecular Biology, National Cancer Institute, NIH
Ira H. Pastan, MD, Co-Chief, Laboratory of Molecular Biology; NIH Distinguished Investigator; Head, Molecular Biology
Section
Immune check point blockade benefits a limited number of patients. SS1P and LMB-100 are immunotoxins used to treat mesothelin expressing cancers. To investigate synergy between check point inhibitors and immunotoxins, we developed a Balb/C
mouse model using mouse breast cancer cells expressing human mesothelin. When immunotoxin was injected into the tumors and anti-CTLA-4 given I.P., anti-tumor immunity developed resulting in complete regressions of injected and distal
un-injected tumors.
2:30 KEYNOTE PRESENTATION: Identifying Mechanisms of Resistance to Antibody-Targeted Cancer Immunotherapy
Louis Weiner, MD, Professor, Oncology and Lombardi Comprehensive Cancer Center, Georgetown University Medical Center
We developed an unbiased in vivo genome-wide RNAi screening platform that leverages host immune selection in strains of immunocompetent and immunodeficient mice to select for tumor cell-based genes that
regulate in vivo sensitivity to immune attack. Utilizing this approach in a syngeneic Triple-Negative Breast Cancer (TNBC) model, we identified 709 genes that selectively regulated adaptive anti-tumor
immunity, and validated the mechanisms that underlie the immune-related effects of expression of these genes in different TNBC lines, as well as tandem synergistic interactions. This approach has utility in identifying unknown tumor-specific
regulators of immune recognition in multiple settings to reveal novel targets for future immunotherapies.
3:00 Chairperson’s Remarks
Paul B. Chapman, MD, Physician & Scientist, Memorial Sloan Kettering Cancer Center
3:05 Loss of Peptide Presentation Apparatus as a Mechanism of Resistance to Checkpoint Inhibitor Therapy
Paul B. Chapman, MD, Melanoma Clinical Director, Attending Physician, Memorial Sloan Kettering Cancer Center;
Professor, Medicine, Weill Cornell Medical College
Since melanoma cells frequently lose expression of HLA alleles, a potentially common mechanism of resistance to checkpoint inhibitors would be loss of antigen processing and presentation machinery. We are evaluating pre- and post-treatment
tumor biopsies for defects in HLA class I antigen processing machinery as a mechanism for resistance to checkpoint inhibitors.
3:35 Refreshment Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
4:25 Understanding Responses to Cancer Therapy: The Tissue is The Issue, but the Scoop is in the Poop
Jennifer Wargo, MD, Melanoma Research, MD Anderson Cancer Center
We have made major advances in cancer therapy through the use of targeted therapy and immunotherapy, however responses are not universal and are not always durable. A better understanding of mechanisms of response and resistance have
been elucidated via analysis of longitudinal tumor and blood samples on therapy – providing potentially actionable strategies to overcome resistance. In addition to this, there is a growing appreciation of the role of the
gut microbiome in modulating systemic and anti-tumor immune responses and insights into the role of the gut microbiome in response to immune checkpoint blockade will be discussed.
4:55 Personalized Cancer Vaccines as a Strategy to Overcome Resistance to Immunotherapy
Zhuting Hu, PhD, Research Fellow, Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School
Clonal evolution of cancer cells can lead to immune evasion, enabling tumors to avoid the attack by the immune response. Neoantigens, which arise from somatic tumor mutations, are highly immunogenic and therefore key targets of tumor
cytolysis in vivo. Personalized cancer vaccines, by targeting a spectrum of different neoantigens expressed by a patient’s tumor rather than a single antigen, can directly address the therapeutic
challenge of tumor clonal heterogeneity and therefore potentially overcome resistance to immunotherapy.
5:25 End of Antibodies for Cancer Therapy
5:30 Registration for Dinner Short Courses* (Commonwealth Hall)
*Separate registration required.