Antibodies have great specificity and potency to be directed against cancer. The latest wave of novel antibody designs leverages our current knowledge of the tumor microenvironment and immune cell populations and our understanding of biology for selective
targeting. Don’t miss the Ninth Annual Antibodies for Cancer Therapy conference for a meeting of the great thought leaders in the field to share creative ideas and advance clinical progress.
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
MONDAY, APRIL 8
7:00 am Registration and Morning Coffee
8:30 Chairperson’s Opening Remarks
Soldano Ferrone, MD, PhD, Division of Surgical Oncology, Surgery, Massachusetts General Hospital
8:40 Using Tumor Reactive mAb and IL2 to Sequentially Engage Innate and Adaptive Anti-Tumor Immunity
Paul M. Sondel, MD, PhD, Reed and
Carolee Walker Professor of Pediatrics, Human Oncology, and Genetics, and Director of Research, UW Division of Pediatric Hematology, Oncology and BMT, UW Carbone Cancer Center and American Family Children’s Hospital, University of Wisconsin
We are developing immunotherapy regimens to eliminate advanced-large immunologically “cold” tumors in immunocompetent mice. In some models, local radiation therapy combined with intratumoral tumor-reactive mAb+IL2 can eradicate large established
tumors with T-cell memory, enabling the tumor to be an in situ vaccine. In mice with two tumors of the same type, immunosuppression from the distant tumor can be overcome by inhibition of Treg cells. Clinical translation
is being pursued.
9:10 Role of HLA Antigen Presentation in Resistance to Immune Checkpoint Blockade
F. Stephen Hodi, MD, Professor,
Medicine, Harvard Medical School; Professor, Medical Oncology, Dana-Farber Cancer Institute; Sharon Crowley Martin Chair, Melanoma, Dana-Farber Cancer Institute
Tumor mutational burden correlates with response to immune checkpoint blockade in multiple solid tumors, although in microsatellite-stable tumors this association is of uncertain clinical utility. Here we uniformly analyzed whole-exome sequencing
(WES) of 249 tumors and matched normal tissue from patients with clinically annotated outcomes to immune checkpoint therapy including radiographic response across multiple cancer types to examine additional tumor genomic features that contribute
to selective response. Our analyses identified genomic correlates of response beyond mutational burden, including somatic events in individual driver genes, certain global mutational signatures, and specific HLA-restricted neoantigens. However,
these features were often interrelated, highlighting the complexity of identifying genetic driver events that generate an immunoresponsive tumor environment. This study lays a path forward in analyzing large clinical cohorts in an integrated and
multifaceted manner to enhance the ability to discover clinically meaningful predictive features of response to immune checkpoint blockade.
9:40 The Next Era of Cancer Therapeutics: Defining Biologic Problems, Engineering Solutions
Daniel Chen, MD, PhD, CMO, IGM
Biosciences
The opportunity for therapeutics that turn on or off a singular target has largely been explored. However, advancements in our understanding of cancer, immune biology, and protein/cellular engineering approaches begin to define what seemed like science
fiction only a few years ago. The spatial temporal coordination of modulating different biologies and cell types within emerging cancer immunotherapy will be explored.
10:10 Networking Coffee Break
10:45 Chairperson’s Remarks
Soldano Ferrone, MD, PhD, Division of Surgical Oncology, Surgery, Massachusetts General Hospital
10:50 Genetic Alteration of the Bispecific Antibody Platform to Create Trispecific NK Cell Engagers (TriKes) Targeting B7-H3
Daniel A. 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. A first-generation TriKE consisting of two antibody scFV fragments each recognizing NK cells and AML cells was cross-linked with cytokine IL-15. Recently,
TriKes have been vastly improved by conversion of the scFVs to camelid framework. We will discuss xenograft studies of first generation TriKE, testing of the improved camelid TriKE, and clinical batch status. We will also discuss TriKEs targeting
B7-H3 for solid tumor therapy.
11:20 Past, Present and Future of Omburtamab for the Treatment of B7H3(+) Tumors
Mahiuddin Ahmed, PhD,
CSO, Y-mAbs Therapeutics
Omburtamab is a murine IgG1 that is under clinical investigation for compartmental radioimmunotherapy of B7-H3(+) tumors. Omburtamab labeled with 131- or 124-Iodine can be delivered directly into 1) the brain ventricles for pediatric neuroblastoma
patients with CNS/leptomeningeal metastases, 2) the pons for diffuse intrinsic pontine glioma, and 3) the peritoneum for desmoplastic small round cell tumors. New versions of omburtamab (177-Lutetium conjugate and humanized sequence) are currently
under pre-clinical development.
11:50 MGC018: A Duocarmycin-Based Antibody Drug Conjugate Targeting B7-H3
Deryk Loo, PhD, Director, Targeted Therapeutics
and Site Operations, MacroGenics, Inc.
MGC018 is an ADC comprised of the cleavable linker-duocarmycin payload, valine-citrulline-seco DUocarmycin hydroxyBenzamide Azaindole (DUBA), conjugated to a humanized anti-B7-H3 antibody through interchain disulfides. MGC018 demonstrated antitumor
activity
in vivo toward B7-H3-expressing tumor xenografts at clinically relevant doses. MGC018 was tolerated in cynomolgus monkeys at exposure levels exceeding those required for antitumor activity. Our findings support
clinical development of MGC018 to evaluate its potential as a therapeutic for B7-H3-expressing solid cancers.
12:20 pm Streamlined Discovery and Production of Therapeutic Antibodies
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Meelis Kadaja, PhD, MBA, Director of Business Development, Icosagen Cell Factory
We take advantage of the universal HybriFree antibody discovery engine to efficiently discover therapeutic antibodies by direct cloning from B-cells of immunized rabbit, chicken, human, or dog. HybriFree method is further powered by our patented QMCF
expression platform to produce high-quality recombinant protein antigens and antibodies cost-effectively for pre-clinical research (including afucosylated antibodies for enhanced ADCC). Technologies and case studies will be presented and discussed.
The talk will present you Biocytogen services for your antibody discovery with case study, from in vivo efficacy and toxicity, to in vitro PD/PD analysis of your antibody candidates, using Biocytogen IO target humanized mouse models, B-NDG
based CART, and PBMC/CD34+ human immune reconstituted mouse models, CD3e humanized models.
1:20 Luncheon Presentation II: Robust and Reproducible Target-Biology Based Bioassays for Characterization and Potency Measurement of Biologics Targeting Checkpoint Modulators
Jane Lamerdin, PhD, Director, Research & Development, Eurofins Pharma Discovery Services
1:50 Session Break
2:20 Problem-Solving Breakout Discussions -Click here for details
3:20 Networking Refreshment Break
4:00 Chairperson’s Remarks
Rakesh Dixit, PhD, DABT, Vice President, R&D, Global Head, Biologics Safety Assessment, Translational Sciences, AstraZeneca
PLENARY KEYNOTE SPEAKER
4:10 Vision for How Immunotherapy Will Shape Future of Cancer Care
Leena Gandhi, MD, PhD, Vice President, Immuno-Oncology Medical Development, Lilly Oncology
Immunotherapy is considered by many as a pillar of cancer care today, but in many ways we have only scratched the surface. Our knowledge and understanding of the complexities of immunotherapy and its mechanisms continue to evolve. The
future of cancer care will be defined by our ability to systematically identify and implement opportunities for combination therapy to improve and standardize patient response.
YOUNG SCIENTIST KEYNOTE
4:55 The Lassa Virus Glycoprotein: Stopping a Moving Target
Kathryn Hastie, PhD, Staff Scientist, Immunology and Microbiology, The Scripps Research
Institute
Lassa virus causes ~5000 deaths from viral hemorrhagic fever every year in West Africa. The trimeric surface glycoprotein, termed GPC, is critical for infection, is the target for neutralizing antibodies, and a major component of vaccines.
Structural analysis of Lassa GPC bound to antibodies from human survivors reveals a major Achilles heel for the virus and provides the needed template for development of immunotherapeutics and improved vaccines.
5:40 Welcome Reception in the Exhibit Hall with Poster Viewing
7:15 End of Day
TUESDAY, APRIL 9
8:00 am Registration and Morning Coffee
8:25 Chairperson’s Remarks
Mitchell Ho, PhD, Chief, Antibody Therapy Section, Laboratory of Molecular Biology, National Cancer Institute, NIH
8:30 A Two-in-One Approach to Target Solid Tumors – CAR T-Cells and Checkpoint Blockade
Prasad
S. Adusumilli, MD, FACS FCCP, Deputy Chief and Associate Attending, Thoracic Surgery; Director, Mesothelioma Program; Head, Solid Tumors Cell Therapy, Cellular Therapeutics Center (CTC), Memorial Sloan-Kettering Cancer Center; Associate
Professor, Cardiothoracic Surgery, Weill Cornell Medical Center
The presentation will focus on cell-intrinsic and extrinsic methods in overcoming checkpoint blockade in cellular immunotherapy.
9:00 Immunotoxins Targeting Mesothelin for Cancer Therapy
Raffit Hassan,
MD, Senior Investigator & Chief, Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, NIH
Mesothelin is a tumor differentiation antigen with limited expression on normal mesothelial cells but is highly expressed in many cancers. LMB-100 is an anti-mesothelin immunotoxin (anti-mesothelin Fab linked to PE toxin) currently in
clinical trials for treating patients with malignant mesothelioma and pancreatic cancer. Our efforts are focused on improving anti-tumor efficacy of LMB-100 by decreasing its immunogenicity as well as combination studies with chemotherapy
and immune checkpoint inhibitors.
9:30 Pancreatic Cancer Therapy with Mesothelin-Redirected Chimeric Antigen Receptor T Cells and Overcoming Barriers to their Efficacy
Mark O’Hara,
MD, GI Malignancy Oncologist, University of Pennsylvania
Pancreatic ductal adenocarcinoma (PDA) is characterized by its highly immunosuppressive tumor microenvironment (TME) that limits T cell infiltration and induces T cell hypofunction. Delivery of mesothelin-redirected chimeric antigen receptor
T cell (meso-CAR T cell) therapy in pancreatic cancer patients has been feasibile and safe, and though some efficacy has been demonstrated, antitumor activity remains modest. Our efforts are focused on improving efficacy of meso-CAR
T cells, including tumor-directed infusion of meso-CAR T cells, genome-editing of CAR T cells, and combining meso-CAR T cells with an oncolytic adenovirus expressing TNF-α and IL-2.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 Chairperson’s Remarks
Horacio G. Nastri, PhD, Senior Director, Antibody Biotherapeutics, Incyte Corporation
10:50 Preclinical Validation of B-Cell Maturation Antigen (BCMA) as a Target for T-Cell Immunotherapy of Multiple Myeloma
Dexiu Bu, MD, PhD, Investigator
III, Exploratory Immuno-Oncology, Novartis Institute for Biomedical Research
Chimeric antigen receptor (CAR) targeting BCMA is an attractive approach for treating multiple myeloma. We screened a set of novel, fully human scFv binding domains to BCMA. Using a series of in vitro and pre-clinical in vivo studies,
we identified a scFv with high specificity for BCMA and robust anti-myeloma activity. This BCMA-specific CAR is currently being evaluated in a Phase Ib clinical study in relapsed and refractory MM patients.
11:20 Tumor-Specific Carbohydrate Antigens as Preferable Targets for Novel Bispecific Immunotherapeutics Targeting Solid Tumors
Anika Jäkel,
PhD, Director, Preclinical Pharmacology & Cancer Immunology, Glycotope GmbH
Carbohydrates on the surface of cancer cells represent preferable targets for bispecifics due to their unique tumor-specificity with lack of inaccessibility on normal tissues and broad indication coverage. We demonstrate that carbohydrates
are valuable targets for different bispecific approaches by creating a carbohydrate-targeted IL-15-based immunocytokine and a bispecific T-cell engager. Both molecules are able to stimulate an array of effector cell responses in vitro and in
vivo and are suitable agents for mono or combinatorial therapy of solid tumors.
11:50 Disrupting the CD47-SIRPα Anti-Phagocytic Axis by a Humanized Anti-CD47 Antibody is an Efficacious Treatment for Malignant Pediatric and Adult Brain Tumors
Sharareh
Gholamin, MD, PhD Candidate, Division of Biology and Biological Engineering, California Institute of Technology
Morbidity and mortality associated with pediatric malignant primary brain tumors remain high in the absence of effective therapies. Macrophage-mediated phagocytosis of tumor cells via blockade of the anti-phagocytic CD47-SIRPα interaction
using anti-CD47 antibodies has shown promise in preclinical xenografts of various human malignancies. We demonstrate the effect of a humanized anti-CD47 antibody, Hu5F9-G4, on five aggressive and etiologically distinct pediatric brain
tumors: group 3 medulloblastoma (primary and metastatic), atypical teratoid rhabdoid tumor, primitive neuroectodermal tumor, pediatric glioblastoma, and diffuse intrinsic pontine glioma. Hu5F9-G4 demonstrated therapeutic efficacy in
vitro and in vivo in patient-derived orthotopic xenograft models. Intraventricular administration of Hu5F9-G4 further enhanced its activity against disseminated medulloblastoma leptomeningeal disease. Notably, Hu5F9-G4 showed
minimal activity against normal human neural cells in vitro and in vivo, a phenomenon reiterated in an immunocompetent allograft glioma model. Thus, Hu5F9-G4 is a potentially safe and effective therapeutic
agent for managing multiple pediatric central nervous system malignancies.
12:20 Luncheon Presentation I: Harbour Biomed’s Fully Human Transgenic HCAb Mouse Technology Presents a Specialized Platform to Develop a New Class of Biologics as Therapeutics Against Cancer And Immunological Diseases
Frank Grosveld, PhD, Founding CSO, Platform Technology, Harbour BioMed
HBM’s transgenic Harbour Mice™ were used to produce Heavy Chain Only Antibodies "HCAbs
" wherein the mouse VH loci were replaced with selected human VH genes, concurrent with the CH1 gene deletion. These refinements give us the flexibility of designing multitude of single molecule formats capable of targeting one or more antigens molecule driven by in vivo biology to develop the NextGen Tx. Here we present one such example of HBM4003, an anti-cancer immunotherapy with high affinity and robust function, currently in preclinical development, leading to potentially exceptional efficacy and safety profile.
12:50 Luncheon Presentation II: Alternative Strategies to Control Light Chain Diversity in Transgenic Chickens
Kathryn Ching, Senior Scientist, Ligand
Shelley Izquierdo, Director, Antibody Discovery, Ligand
OmniChicken® V gene diversity in B cells can be controlled through rational design of synthetic pseudogenes inserted into the Ig loci. One design, for the purpose of conventional HxL antibodies, results in extensive diversity focused
in CDR regions, and the other design, for the purpose of common light chain antibody development, results in minimal diversity across the entire V region.
1:20 Ice Cream Break in the Exhibit Hall with Poster Viewing
2:00 Chairperson’s Remarks
Mitchell Ho, PhD, Chief, Antibody Therapy Section, Laboratory of Molecular Biology, National Cancer Institute, NIH
2:05 Anti-BCMA Recombinant Immunotoxins Are Highly Active Agents for Myeloma Therapy
Ira H. Pastan, MD, Co-Chief,
Laboratory of Molecular Biology; NIH Distinguished Investigator; Head, Molecular Biology Section
BCMA is highly expressed in myeloma cells and is an excellent target for myeloma therapy. We produced mAbs that recognize BCMA, but not other family members, and used them to make RITs that kill myeloma cell lines and patient cells. To
evaluate anti-tumor activity, we prepared H929 cells expressing luciferase. Untreated mice survived 40 days, whereas treated mice were tumor-free at 90 days.
2:35 Immune-Based Therapies in AML/MDS
Naval G. Daver, MD,
Associate Professor, Leukemia Department, MD Anderson Cancer Center
3:05 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.
3:20 Next Generation of Antibody Drugs with Long Lasting Efficacy
Le Sun, PhD, CEO & President AbMax Biotechnology Co., Ltd.
In this presentation, we will show 1) the successful development of Me-better by removing the strong B-cell epitopes in the FRs of Humira; 2) the improvement of stability and great reduction of in vivo ADA by engineering the Fc of Tecentriq's with better biological activity.
3:35 Refreshment Break in the Exhibit Hall with Poster Viewing
Chairperson’s Remarks
Mitchell Ho, PhD, Chief, Antibody Therapy Section, Laboratory of Molecular Biology, National Cancer Institute, NIH
4:25 Development of Next Generation Immune Modulators
René Hoet, PhD, CSO,
Imcheck Therapeutics
Imcheck Therapeutics, an emerging biotech, develops antibodies to novel targets in immuno-oncology and potentially autoimmune diseases. The presentation will cover the progress of development of two first-in-class therapeutic antibodies
(an anti-BLTA and an anti-BTN3) that have a positive effect on proliferation of gamma delta T cells and inhibition of tumor growth that are developed towards the clinic in 2020. In addition, the company identified an additional set
of novel targets that are in the antibody validation stage for treatment in immune-oncology and potentially autoimmunity.
4:55 Phase I CD123 CAR T Cell Trial in Adults with Relapsed/Refractory AML
Elizabeth
Budde, MD, PhD, Assistant Professor, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope
5:25 Strategies and Challenges for Targeting CD47 to Enhance Antitumor Immunity
David D. Roberts, PhD, Senior Investigator, Head, Biochemical Pathology Section, Laboratory of Pathology, CCR, NCI
The resistance of many cancers to current immune checkpoint inhibitors might be overcome by identifying additional checkpoint molecules that enable tumors to evade immune surveillance. CD47 is a ubiquitously expressed receptor for thrombospondin-1
and the counter-receptor for signal-regulatory protein-α. The latter interaction prevents innate immune clearance of tumor cells that express elevated levels of CD47. Preclinical and clinical development of antibodies and other
methods for targeting CD47 will be discussed.
5:55 End of Antibodies for Cancer Therapy: Driving Breakthrough Therapies
5:30 Registration for Dinner Short Courses