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Showing of Streams
12:10pm - 1:25pm

Networking Luncheon

Showing of Streams
5:00pm - 5:05pm
Close of Conference

Close of Conference

8:25am - 8:30am 5 mins
Track 1: Novel Engineering Strategies to Enhance Antibody Functions
Chairman’s Remarks
  • Chairman Paul Carter, PhD - Senior Director and Staff Scientist, Antibody Engineering, Genentech, Inc.
more
8:25am - 8:30am 5 mins
Track 2: Immuno-Oncology: Checkpoints
Chairman’s Remarks
  • Chairman James Larrick, M.D., Ph.D. - Managing Director and Chief Medical Officer, Velocity Pharmaceutical Development, Panorama Research, Inc.
more
8:30am - 9:00am 30 mins
Track 1: Novel Engineering Strategies to Enhance Antibody Functions
Agonizing the TNFR Superfamily for Cancer Immunotherapy
  • Greg Lazar, Ph.D. - Director and Senior Scientist, Antibody Engineering Department, Genentech Inc
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Multiple technology platforms have been explored to enable antibodies to mediate receptor agonist activity without relying on Fc receptor-mediated crosslinking. This talk will describe engineering approaches and considerations, present data demonstrating in vitro and in vivo proof of concept, and discuss biological and clinical context as they relate to cancer immunotherapy.

8:30am - 9:00am 30 mins
Track 2: Immuno-Oncology: Checkpoints
BAG3 A Potential Target for Pancreatic Adenocarcinoma Treatment
  • Vincenzo De Laurenzi, M.D., Ph.D. - Associate Professor in Clinical Biochemistry and Molecular Biology, Department of Biomedical Sciences, Universita' "G. d'Annunzio" Chieti-Pesca
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Death rate of Pancreatic Ductal Adenocarcinoma (PDAC) has increased in recent years, therefore the identification of novel therapeutic targets is essential. We have data showing that PDAC cells secrete BAG3 that binds and activates macrophages trough a specific receptor (IFITM2), inducing their activation and the secretion of citokines (including IL-6) that promote PDAC growth. We also show in xenograft models that treatment with a murine monoclonal antibody against BAG3 reduces tumor growth and impairs metastasis formation. We have also generated a humanized variant of this antibody by grafting Complementarity Determining Regions (CDR)s from the murine into a human antibody framework using a computer assisted molecular modelling. We also show that the humanized antibody has the ability to inhibit macrophage activation in vitro and reduce tumor growth in xenograft models to an extent comparable to the murine parental antibody. Finally we tested the anti BAG3 antibody in combination with anti PD-1 antibody and observe a significant additive effect. In conclusion, we have identified a novel paracrine loop that sustains PDAC growth and metastatic spreading and show that its blockage with an humanized anti-BAG3 antibody has therapeutic potential for treatment.

9:00am - 9:30am 30 mins
Track 1: Novel Engineering Strategies to Enhance Antibody Functions
Isoelectric Point Engineering to Enhance the Potency of pH Dependent Antigen Binding Antibody
  • Taichi Kuramochi - Research Scientist, Chugai Pharmabody Research Pte. Ltd.
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Previously, isoelectric point engineering was used to improve pharmacokinetics and physicochemical property of antibody therapeutic. We found that isoelectric point engineering in variable region and constant region can applied to enhance the potency of pH dependent antigen binding antibody. Case study will be presented.

9:00am - 9:30am 30 mins
Track 2: Immuno-Oncology: Checkpoints
SIMPLE Antibody™ Platform Generates Unique Species Cross-reactive Antibodies against Immune Checkpoints
  • Erik Hofman, Ph.D. - Senior Scientist, Research Department, Argenx
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Clinical lead candidate antibodies often lack species cross-reactivity, necessitating the development of substitute antibodies for pre-clinical development in mice or monkeys. Using argenx’ SIMPLE Antibody™ platform we were able to generate functional human-mouse cross-reactive antibodies against several validated immune checkpoint proteins, including PD-1, VISTA and LAG-3. We will present in vitro and in vivo data of our antibodies to demonstrate their unique features.

9:30am - 10:00am 30 mins
Track 1: Novel Engineering Strategies to Enhance Antibody Functions
Adapted Fc-glycan changes for enhanced ADCC and/or CDC
  • Gestur Vidarsson, Ph.D. - Head of Immunoglobulin Research/PI, Experimental Immunohematology, Sanquin Research
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Glycosylation of the immunoglobulin G (IgG)-Fc tail is required for binding to Fc-gamma receptors (FcγRs) and complement-component C1q. Here we show that the not only afucosylated IgG1 antibodies, but more prominent combination of afucosylation and hypergalactosylation increases FcγRIIIa and FcγRIIIb by ~20-fold on top of the ~17-fold achieved by afucosylation alone. This increased binding is accompanied with similarly enhanced ADCC. On top of this, we convincingly show that elevated galactosylation also increased C1q-binding and downstream complement opsonization and CDC. In conclusion, antibodies can be tailored by natural glycan changes to have either enhanced CDC or ADCC, or both.

9:30am - 10:00am 30 mins
Track 2: Immuno-Oncology: Checkpoints
Targeting Immunosuppressive Myeloid Cells to Enhance Cancer Immunotherapy
  • Xin Lu, Ph.D. - John M. and Mary Jo Boler Assistant Professor, Department of Biological Sciences, University of Notre Dame
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Targeted therapy against myeloid-derived suppressor cells (MDSCs), using multikinase inhibitors such as cabozantinib and dactolisib, can synergize with immune checkpoint blockade antibodies (anti-CTLA4, anti-PD1) to eradicate metastatic castration-resistant prostate cancer.

10:00am - 10:30am 30 mins
Track 1: Novel Engineering Strategies to Enhance Antibody Functions
Networking Refreshment Break
10:00am - 10:30am 30 mins
Track 2: Immuno-Oncology: Checkpoints
Networking Refreshment Break
10:30am - 11:00am 30 mins
Track 1: Novel Engineering Strategies to Enhance Antibody Functions
From Format to Function - Engineering Transformative Antibodies
  • Martin Steegmaier, Ph.D. - Head of Discovery, Large Molecule Research, Roche Pharma Research and Early Development, Roche Innovation Center Munich
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Bi- and multispecific antibodies enable the exploration of new biological concepts and treatment strategies. Within Roche such next generation biologics have found broad application prospects in onco-immunological and anti-inflammatory approaches. But their use goes far beyond these established applications to convey unique mode of actions. The CrossMAb technology has proven to be very versatile, allowing the generation of various bispecific antibody formats ranging from heterodimeric/asymmetric bivalent 1+1 CrossMAbs to more complex tri- (2+1), tetravalent (2+2) bispecific and multispecific antibody formats. Examples given will include new bispecific molecules for cancer immunotherapy and the use of novel targeting approaches to treat neurological disorders. The DutaFab technology platform brings forward a novel class of fully human monoclonal antibody drugs that bind any two antigens with high affinity and specificity. DutaFabs have a unique, proprietary CDR design with two independent paratopes within the natural human CDRs. DutaFabs have been found to be extremely stable and well behaved molecules and are therefore particularly well suited to be injected into the eye for treating burdensome diseases such as macular degeneration or diabetic retinopathy. The latest developments of the DutaFab -enabled antibody formats and applications will be reviewed.

10:30am - 11:00am 30 mins
Track 2: Immuno-Oncology: Checkpoints
A Novel Cytokine Receptor Agonistic Antibody by Design
  • Cheng-I Wang, Ph.D. - Senior Principal Investigator, Singapore Immunology Network, Biomedical Sciences Institutes, ASTAR
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A key feature of effective cancer immunotherapy relies on enhanced anti-tumor immune response and reduced suppressive effects. As natural cytokines are made to maintain balance between activation and suppression, they are often unable to achieve desired therapeutic efficacy. Here we describe the design of a cytokine receptor agonist antibody that mimics IL-2’s immune stimulatory effects on CD8 T cells with minimal Treg activation.

11:00am - 11:30am 30 mins
Track 1: Novel Engineering Strategies to Enhance Antibody Functions
Tumor Uptake of PEGylated Diabody: Balancing between Antibody Size and Systemic Clearance
  • Qing Li, Ph.D. - Scientist I, MedImmune
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Antibody tumor targeting is a complex process involving many factors such as antibody size, distribution and clearance in the plasma. Antibody fragments with optimal profile balanced between size and systemic clearance hold potential for diagnostic and therapeutic applications of tumor malignancies. This talk focuses on the investigation of the correlation of hydrodynamic size, pharmacokinetic parameters and tumor uptake of PEGylated diabody.

11:00am - 11:30am 30 mins
Track 2: Immuno-Oncology: Checkpoints
Cow Ultralong CDR3 Antibodies Targeting Exhausted T-cells
  • Vaughn Smider, M.D., Ph.D. - Assistant Professor, Molecular Medicine, The Scripps Research Institute
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Cow antibodies have unusually long CDR3 regions. We have characterized the genetic and structural properties of these antibodies, and have identified novel antibodies against HIV and exhausted T-cell targets.

11:30am - 12:00pm 30 mins
Track 1: Novel Engineering Strategies to Enhance Antibody Functions
Targeting Ebola with Bispecific Antibodies
  • Kartik Chandran, PhD - Professor of Microbiology and Immunology, Harold and Muriel Block Faculty Scholar in Virology, Albert Einstein College of Medicine
more
11:30am - 12:00pm 30 mins
Track 2: Immuno-Oncology: Checkpoints
ILC-mediated Regulation of Tumor-associated T cells: Implications for Immunotherapy
  • Sarah Crome, Ph.D. - Banting Postdoctoral Fellow, Princess Margaret Cancer Centre, University Health Network
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We recently identified a unique innate lymphoid cell (ILC) population that suppresses the expansion and function of tumor-associated T cells, and is associated with early recurrence in high-grade serous cancer. This regulatory ILC population has properties that overlap with Natural Killer cells and other defined ILCs, yet can be differentiated by a distinct gene expression signature. Current studies are defining molecular interaction that control regulatory ILC function and identifying ways to target this population to enhance immunotherapies.

12:10pm - 1:25pm 75 mins
Networking Luncheon
1:25pm - 1:30pm 5 mins
Track 1: Role of the T-Cell Repertoire in Cancer, Infectious Diseases and Autoimmunity
Chairwoman’s Remarks
  • Chairwoman Jamie Scott, M.D., Ph.D. - Professor and Canada Research Chair in Mol. Immuni., Molecular Biology & Biochemistry, Simon Fraser University
more
1:25pm - 1:30pm 5 mins
Track 2: Innovating Antibody Therapeutics
Co-Chairs' Remarks
  • Co-Chair Paul Parren, Ph.D. - Professor, Department of Immunohematology and Blood Transfusion, Leiden University Medical Center
  • Co-Chair William Strohl, Ph.D. - Owner and President, BiStro Biotech Consulting LLC
more
1:30pm - 2:00pm 30 mins
Track 1: Role of the T-Cell Repertoire in Cancer, Infectious Diseases and Autoimmunity
Mining Shared Neoantigen-Specific TCRs From Healthy Donors for Tailored Cancer Immunotherapy
  • Mark Cobbold, M.D., Ph.D. - Associate Professor of Medicine, Center for Cancer Immunology, MGH Cancer Center
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There is a marked collapse of our TCR repertoire as we age resulting in a physiological immunodeficiency that compromises the immunosurveillance of infectious and malignant disease. As we enter an age of living drugs it becomes possible to mine TCRs from immunocompetent healthy donors for TCRs reactive against shared neoantigens. Using a proteomic approach, we identify shared surface HLA-bound neoantigens and characterize TCRs against these suitable for immunotherapeutic translation.

1:30pm - 2:00pm 30 mins
Track 2: Innovating Antibody Therapeutics
Computationally-driven Identification of Antibody Epitopes
  • Chris Bailey-Kellogg, PhD - Professor, Computer Science, Dartmouth University
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The identification of where and how antibodies recognize antigens can help define and distinguish mechanisms of action, provide insights into progression of immune responses, and facilitate targeted development of vaccines and therapeutic antibodies. An antibody’s amino acid sequence implicitly encodes specific recognition of its antigen, and here we investigate the extent to which this information can be leveraged to localize epitopes. We have developed a method, EpiScope, which uses computational methods to hypothesize antibody-antigen binding modes and design targeted panels of antigenic variants to test these hypotheses via antibody binding assays. In prospective studies of two antibodies against tumor antigen B7H6, this integrated computational-experimental approach successfully localized epitopes with a designed panel of five or fewer antigenic variants for each antibody, or alternatively, a six-variant panel for both simultaneously. This use of antibody sequence to drive strikingly efficient epitope localization likely holds more generally; for 29 of 33 distinct antibody-antigen pairs in a retrospective analysis, designed panels required an average of only three antigenic variants to include one or more mutations likely to disrupt binding according to co-crystal structures. There is likewise general promise for design of antigen panels able to efficiently probe multiple antibody epitopes: an integrated four-variant panel designed to map twelve antibodies against vaccinia virus D8 revealed groups of specificities matching experimental binning studies, and contained mutations predicted to disrupt binding of members of each group. We conclude that computational modelling and antigen variant design reveal key determinants of antibody-antigen binding that enable effective epitope localization experiments.

2:00pm - 2:30pm 30 mins
Track 2: Innovating Antibody Therapeutics
Evolution of Antibodies of Different Germline Gene Origins Proceed through Different Paths
  • Mats Ohlin, Ph.D. - Professor, Department of Immunotechnology & SciLifeLab, Lund University
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The variable domains of antibodies evolve in vivo, or are evolved in the laboratory, to achieve high-affinity interaction between its binding site and its epitope, thereby also in many cases achieving improved functional properties of the antibody. Affinity maturation of an antibody’s variable domains is achieved by modification of key residues in the context of a framework that provide the stable basic fold of the domains. This process has to target the evolvable parts of the domains, mostly considered as the complementarity determining regions (CDR), but ought to leave other parts, the framework regions (FR) largely untouched. The outcomes in terms of positive selection of in vivo evolution is often interpreted in terms of patterns of silent and replacement-type mutations in these regions. Indeed, in vitro affinity maturation often implies evolution of sequences in complementarity determining regions. We hypothesized that preferred evolution patterns, in vivo and in vitro, may rather reflect the combined features of CDR and FR and that antibodies of different germline gene origins may have different possibilities in terms of paths forward in an evolution process.

2:30pm - 3:00pm 30 mins
Track 1: Role of the T-Cell Repertoire in Cancer, Infectious Diseases and Autoimmunity
CD39 and CD103 Identify Tumor-reactive CD8 T cells in Human Solid Tumors
  • Thomas Duhen, Ph.D. - Senior Research Scientist, AgonOx
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Identification of tumor-reactive CD8 T cells is key to better understand how antibody-mediated immunotherapies work in cancer patients and to improve success for adoptive T cell therapy. Here we identified a subset of tumor-infiltrating CD8 T cells (CD8 TIL) characterized by co-expression of CD103 and CD39 in human solid tumors. This cell population, which is specifically enriched at primary and metastatic tumor sites, appeared to be chronically stimulated and displayed characteristics of tissue-resident memory T cells. Importantly, these cells had a very distinct TCR repertoire as compared to other CD8 TIL subsets, and had the ability to kill autologous tumor cells in vitro. Finally, a higher frequency of those cells in human head and neck tumors correlated with a greater overall survival. Collectively, our findings are an important advance in the biology of tumor-reactive CD8 T cells and will help develop new therapeutics especially in patients with low frequencies of these cells.

2:30pm - 3:00pm 30 mins
Track 2: Innovating Antibody Therapeutics
DNA-based Antibody Therapy via Antibody Gene Transfer
  • Kevin Hollevoet, Ph.D. - Group Leader and Postdoc, Therapeutic and Diagnostic Antibodies, University of Leuven
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Recombinant antibodies are one of today’s most successful therapeutic classes in the field of inflammatory diseases and oncology. A wider accessibility and implementation, however, is hampered by high production costs, prolonged need for frequent administration, and adverse events. Moreover, the often limited therapeutic efficacy as a single agent has led to a surge in (antibody) combination therapies, which adds to the cost and risk of toxicity. The Antibody Gene Transfer Program, a young research branch within the Laboratory for Therapeutic and Diagnostic Antibodies, is dedicated to advancing DNA-based antibody therapy. This approach seeks to administer to patients the antibody-encoding DNA sequences, rather than the antibody proteins, thereby allowing the body to produce its own medicine. The current presentation provides a comprehensive overview of our Research Program, and illustrates how in vivo antibody expression can address several of the difficulties surrounding conventional antibody protein therapy. A selection of our pre-clinical work on the in vivo expression of tumor-targeting and immunomodulatory antibodies via gene electrotransfer is presented. Finally, opportunities and hurdles towards clinical application are discussed.

3:00pm - 3:30pm 30 mins
Track 1: Role of the T-Cell Repertoire in Cancer, Infectious Diseases and Autoimmunity
Networking Refreshment Break
3:00pm - 3:30pm 30 mins
Track 2: Innovating Antibody Therapeutics
Networking Refreshment Break
3:30pm - 4:00pm 30 mins
Track 1: Role of the T-Cell Repertoire in Cancer, Infectious Diseases and Autoimmunity
Discovery of Potent Anti-Tumor TCRs in Recombinant TCR Libraries Generated from Tumor Infiltrating Lymphocytes
  • David Johnson, PhD, MBA - Founder and CEO, GigaMune, Inc.
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Autologous tumor infiltrating lymphocytes (TILs) expanded ex vivo have shown high clinical efficacy in metastatic melanoma patients and are being actively investigated in additional solid tumors including ovarian, cervical, renal cell, and non-small cell lung cancer. TILs provide anti-tumor reactivity by recognizing tumor-specific mutations and aberrantly expressed tumor-associated antigens (TAAs). The T cell receptor (TCR) clonotypes in TILs could be mined for anti-cancer TCRs to form the basis of novel cell therapies, but conventional methods for TCR characterization are relatively low-throughput, hampering progress. Our high-throughput single cell droplet microfluidic technology captures and physically links natively paired TCRab clonotypes from millions of cells in an hour. We used our technology to generate natively paired TCRab libraries from five clinically efficacious melanoma TIL infusion products. Deep sequencing of these “recombinant TIL” libraries gave 19,000-50,000 unique clonotypes for each of the TIL infusion products with clonotype frequencies slightly higher than seen in healthy donor PBMC samples. We cloned these TCRab libraries en masse into lentiviral expression libraries, expressed them in the TCRb negative Jurkat cell line (J.RT3-T3.5), and screened for reactive TCRs targeting known public tumor peptide:MHC antigens. In one successful effort, we identified five rare TCR clonotypes (≤0.1% each in the starting TIL library) from an HLA-A*02:01 positive patient that bound to an HLA-A*02:01 dextramer loaded with gp100154-162 (PMEL17) peptide. These monoclonal TCRab sequences specifically induced cellular activation when co-cultured with gp100 peptide-pulsed T2 cells and A2(+) melanoma cells whereas mis-paired TCRs were not reactive. To our knowledge, we have generated the largest-ever natively paired recombinant TCRab libraries, and we are also the first group ever to make recombinant TIL libraries and mine them for anti-tumor TCRs. Unlike primary T cell samples, our recombinant TIL libraries are immortal and can be repeatedly mined for TCRs reactive against any peptide antigen target. Future work will involve development of TIL-derived TCRs for solid tumor cellular therapy.

3:30pm - 4:00pm 30 mins
Track 2: Innovating Antibody Therapeutics
Structural Determinants for Modulating Antibody-Fc Receptor Interactions for Half-Life Enhancement and Effector Functions
  • Karthik Viswanathan, Ph.D. - Director, Research, Visterra, Inc.
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Engineering of antibodies for enhanced binding to neonatal Fc receptor (FcRn) and improved pharmacokinetics has been demonstrated in humans and other primates. The approaches used to identify the Fc variants have largely relied on random mutagenesis and display formats, which have often led to compromises in other critical attributes of the antibody, including effector functions and biophysical stability. We have developed a structure- and network-based framework to interrogate the engagement of IgG with multiple Fc receptors (FcRn, C1q, TRIM21, FcγRI, FcγRIIa/b, FcγRIIIa). Using this framework, we identified structural features that govern Fc-FcRn interaction, thereby providing multiple distinct pathways to engineer enhanced antibody engagement with FcRn. We augmented our structural analysis with amino acid interaction networks, which provided insights into allosteric consequences of mutations that would have been overlooked by conventional structural analyses. Applying these principles, we have engineered a panel of novel Fc variants, including combinations of mutations, which enhance pH-dependent FcRn binding and retain robust biophysical properties and native binding to Fcγ receptors. Multiple antibodies harboring these Fc variants exhibit half-life improvement in various animal models (>9-fold in some instances) while maintaining robust effector functions, including ADCC, CDC and ADIN mediated by TRIM21.

4:00pm - 4:30pm 30 mins
Track 1: Role of the T-Cell Repertoire in Cancer, Infectious Diseases and Autoimmunity
Genetic Variation in MHC Proteins is Associated with T-cell Receptor Expression Biases
  • Eilon Sharon, Ph.D. - Postdoctoral Research Fellow, Genetics, Howard Hughes Medical Institute, Stanford University
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In each individual, a highly diverse T cell receptor (TCR) repertoire interacts with peptides presented by major histocompatibility complex (MHC) molecules. Despite extensive research, it remains controversial whether germline-encoded TCR–MHC contacts promote TCR–MHC specificity and, if so, whether differences exist in TCR V gene compatibilities with different MHC alleles. We applied expression quantitative trait locus (eQTL) mapping to test for associations between genetic variation and TCR V gene usage in a large human cohort. We report strong trans associations between variation in the MHC locus and TCR V gene usage. Fine-mapping of the association signals identifies specific amino acids from MHC genes that bias V gene usage, many of which contact or are spatially proximal to the TCR or peptide in the TCR–peptide–MHC complex. Hence, these MHC variants, several of which are linked to autoimmune diseases, can directly affect TCR–MHC interaction. These results provide the first examples of trans-QTL effects mediated by protein–protein interactions and are consistent with intrinsic TCR–MHC specificity.

4:00pm - 4:30pm 30 mins
Track 2: Innovating Antibody Therapeutics
Characterization of Circulating Antibodies Using Next Generation Sequencing and Mass Spectrometry
  • Natalie Castellana, PhD - Chief Executive Officer, Digital Proteomics LLC
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Deep sequencing of peripheral blood mononuclear cells (PBMCs) has recently provided the ability to characterize a snapshot of the complex immunoglobulin repertoire. This sequenced antibody repertoire provides a wealth of information, but is a poor proxy for circulating antibodies. Direct interrogation of serum antibodies using mass spectrometry provides a complementary view of the immune response. We employ a proteogenomic approach integrating sequenced antibody transcripts from multiple tissue types with purified serum antibodies from a rabbit immunization experiment. We compare repertoires across time points and tissue origins. Furthermore, our proteogenomic platform enables us to perform antibody discovery and identify candidates directly from serum.

4:30pm - 5:00pm 30 mins
Track 1: Role of the T-Cell Repertoire in Cancer, Infectious Diseases and Autoimmunity
Dynamics of the T cell Repertoire during Multiple Episodes of Hepatitis C Virus Infection
  • Naglaa Shoukry, Ph.D. - Professor, Department of Medicine, Director, Viral Hepatitis Research Group, University of Montreal
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The dynamics of the CD8 T cell receptor (TCR) repertoire and factors governing the selection of TCR clonotypes conferring protective immunity in real life settings are poorly understood. I will present our analysis of the dynamics and functionality of the hepatitis C virus (HCV)-specific CD8 TCR repertoire before, during and after primary infection and reinfection in relation to long-term protection against viral persistence.

4:30pm - 5:00pm 30 mins
Track 2: Innovating Antibody Therapeutics
Analysis of the Current Antibody Landscape and Meeting Highlights
  • William Strohl, Ph.D. - Owner and President, BiStro Biotech Consulting LLC
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This presentation provides an overview of current publicly available clinical stage antibodies, Fc fusion proteins, and CAR constructs, of which there are currently over 800 examples.  Different strategies and methods for addressing the 300-plus unique target antigens will be compared and contrasted.  Additionally, the various strategies for using antibody-based constructs, including Fc engineered IgGs, bispecific approaches, ADCs, and CARs, will be covered on a target group basis.  Finally, the presentation will cover significant highlights from the current meeting and integrate those highlights into the current and future state of antibody-based drugs.

5:00pm - 5:05pm 5 mins
Close of Conference