The Antibody Society

the official website of the antibody society

An international non-profit supporting antibody-related research and development.

Novel engineering strategies to enhance antibody functions

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Please join us at the Society’s annual meeting, Antibody Engineering & Therapeutics, on December 11-15, 2017 at the Manchester Grand Hyatt, San Diego, CA! Here, Paul J. Carter, Ph.D., Senior Director and Staff Scientist, Antibody Engineering, Genentech, discusses what you will learn in his session on novel engineering strategies to enhance antibody functions, which will be held on Friday December 15, 2017.

A recurring theme with this conference since it began in the early 1990s has been the presentation of new antibody engineering technologies and their application to the design of antibodies for specific clinical applications. True to this tradition, this session will showcase a broad range of different antibody platform technologies for improving existing antibody properties or engineering antibodies with brand new capabilities. Antibody technologies to be highlighted include bispecific antibodies in many different formats, PEGylation, glyco-engineering and engineering of isoelectric point (pI).

Greg Lazar (Genentech) will present on agonizing the TNFR superfamily independent of FcgR-mediated cross-linking using multiple antibody technology platforms. This talk will highlight in vitro and in vivo proof-of-concept data. Taichi Kuramochi (Chugai Pharmabody Research) will provide a case study on pI engineering of an antibody variable domains and constant regions to enhance the potency of pH-dependent antigen binding antibody. Gestur Vidarsson (Sanquin Research) will describe how the natural glycans of antibodies can be tailored to increase ADCC and/or CDC activities. For example, combining hypergalactosylation with afucosylation increases the potency of ADCC activity beyond that achieved by afucosylation alone.

After the networking break, Martin Steegmaier (Roche Innovation Center Munich) will discuss applications of CrossMAbs in bivalent (1+1), trivalent (2+1) and tetravalent (2+2) formats for cancer immunotherapy and the use of novel targeting approaches for neurological diseases. Additionally, bispecific antibodies in DutaFab format for ophthalmologic diseases will be described.  Qing Li (Medimmune) will demonstrate tumor uptake of a PEGylated antibody fragment. Specifically, this presentation will focus on investigation of the correlation between hydrodynamic size, pharmacokinetic parameters and tumor uptake of a PEGylated diabody. Kartik Chandran (Albert Einstein College of Medicine) will close the session by presenting a bispecific antibody “Trojan horse” approach for broad protection against ebolaviruses. One arm of the bispecific antibody binds a conserved epitope on ebolavirus glycoprotein. After internalization of the virus/antibody complex into cells and trafficking to late endosomes, the second arm of the bispecific blocks infection by binding to the viral entry receptor, NPC1.

Interested in attending the meeting? Society members can save 15% on the registration fee! Contact us at membership@antibodysociety.org for the code.

Not a member? Please join!

Membership is free for students and employees of the Society’s corporate sponsors.

The Antibody Society joins FOCIS!

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We are pleased to announce that The Antibody Society is now a Member Society of the Federation of Clinical Immunology Societies (FOCIS), which exists to improve human health through immunology by fostering interdisciplinary approaches to both understand and treat immune-based diseases. By joining FOCIS as a Member Society, our network has expanded to include over 60,000 clinicians and basic researchers dedicated to a cross-disciplinary approach to immunologic disease.

Information about Member Society and Individual Membership benefits, education opportunities, FOCIS publications and the FOCIS Member Society Roster can be found here. We look forward to working with FOCIS to achieve the goals shared by our organizations.

IMMUNO-ONCOLOGY: CHECKPOINTS

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The Antibody Society invites you to attend its annual meeting, Antibody Engineering & Therapeutics, on December 11-15, 2017 at the Manchester Grand Hyatt, San Diego, CA! In this summary, chairperson James Larrick, M.D., Ph.D., Managing Director and Chief Medical Officer, Panorama Research Institute and Velocity Pharmaceutical Development, discusses what you will learn at his session on immune-oncology checkpoints, which will be held on Friday December 15.

The management of cancer has dramatically changed over the past decade with the introduction of novel immunotherapies, chief among them inhibitors of checkpoint receptors — molecules whose function is to restrain the host immune response.  Antibodies inhibiting CTLA4 and PD1-PD-L1 have shown remarkable clinical benefit.  The field is evolving rapidly, with many clinical trials testing novel checkpoint inhibitors (e.g., anti-LAG3, anti-TIM3), alone, in combination, or with other targeted therapies. A sampling of novel approaches will be covered in this symposium.

This Friday morning (December 15, 2017) session will be led off by Mickey Hu (Panorama Institute of Molecular Medicine) who has developed a series of novel immunomodulatory drugs that suppress PD-L1 expression in tumor cells and inhibit the PD-L1/PD-1 checkpoint, resulting in the recruitment of natural killer (NK) cells into the tumor microenvironment that leads to tumor suppression. Efforts to combine immunomodulatory drugs with checkpoint blockades to overcome difficult-to-treat cancers with tolerable side effects will be described.

Clinical lead candidate antibodies often lack species cross-reactivity, necessitating the development of substitute antibodies for pre-clinical development in mice or monkeys. Next, Erik Hofman, (Argenx) will describe the use of the SIMPLE Antibody platform to generate functional human-mouse cross-reactive antibodies against several validated immune checkpoint proteins, including PD-1, VISTA and LAG-3.

Xin Lu (University of Notre Dame) will present data indicating that targeted therapy against myeloid-derived suppressor cells, using multikinase inhibitors such as cabozantinib and dactolisib, can synergize with immune checkpoint blockade antibodies (e.g., anti-CTLA4, anti-PD1) to eradicate metastatic castration-resistant prostate cancer.

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 a balance between activation and suppression, they are often unable to achieve desired therapeutic efficacy. Cheng-I Wang (Biomedical Sciences Institutes, ASTAR, Singapore) will describe a cytokine receptor agonist antibody that mimics IL-2’s immune stimulatory effects on CD8 T cells with minimal Treg activation.

Cow antibodies have unusually long CDR3 regions. Vaughn Smider (The Scripps Research Institute) has characterized the genetic and structural properties of these antibodies, and has identified novel antibodies against HIV and exhausted T-cell targets utilizing this approach.

The final speaker, Sarah Crome, (Princess Margaret Cancer Centre, University Health Network, Canada) will describe efforts to characterize 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 cancer. This regulatory ILC population has properties that overlap with NK cells and other defined ILCs, yet can be differentiated by a distinct gene expression signature. Studies defining molecular interactions that control regulatory ILC function and ways to target this population to enhance immunotherapy will be presented.

Interested in attending the meeting? Society members can save 15% on the registration fee!

Not a member? Please join!

Membership is free for students and employees of the Society’s corporate sponsors.

Biological Impact of Fc Receptor Engagement

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Please join us at the Society’s annual meeting, Antibody Engineering & Therapeutics, on December 11-15, 2017 at the Manchester Grand Hyatt, San Diego, CA! In this summary, session organizers Trudi Veldman (Senior Director Biologics, AbbVie Bioresearch Center) and Chung-Ming Hsieh (Executive Director, Biologics Discovery Boston, Merck & Co.) discuss what you will learn at their session ‘Biological Impact of Fc Receptor Engagement’, which will be chaired by Chung-Ming Hsieh on Thursday December 14.

Antibodies are both binding proteins to their cognate targets and bridging molecules to downstream biological pathways via interaction with the various Fc receptors (e.g., FcγR and FcRn), complement, and lectins.  While our efforts in understanding the biology of therapeutic antibodies are often initially focused on the variable domain and target engagement, e.g., binding kinetics, potency, epitopes, it is crucial that we also gain understanding of the biology of the constant region of a therapeutic antibody and its impact on efficacy and safety.

This session aims to strengthen our current understandings on the biological impact of Fc receptor engagement.  The first presentation by Kenta Haraya (Chugai) will discuss the generation and characterization of a novel IgG1 Fc variant with optimized binding to FcRn that does not have increased binding by rheumatoid factors.  This Fc variant has been incorporated into a recycling antibody being developed for complement-mediated diseases.

The next three presentations will focus on the impact of FcγR engagement on antitumor activities of protein therapeutics.  Rony Dahan (Rockefeller) will present the finding that the antitumor activity of a human CD40 agonistic antibody is dependent on FcγRIIb engagement and is inhibited by FcγRIIa engagement, highlighting the importance of Fc domain optimization for improved efficacy.  Moving beyond antibodies, Daniel Christ (Garvan Institute of Medical Research) will present data indicating that the potent antitumor activity of interleukin-2-Fc fusion protein requires Fc-mediated depletion of regulatory T-cells.  Lastly, Frederick Arce Vargas (University College London Cancer Institute) will present the depletion of tumor-infiltrating regulatory T cells by an Fc-optimized anti-CD25 in synergy with PD-1 blockade to eradicate established tumors.

The field also continues to make progress in engineering Fc for modulating antibody effector functions, FcγR or complement engagement, and circulating half-life.  To this end, James Ernst (Genentech) will present effector function-attenuating mutations that maintain antibody stability and reduce toxicity.  George Georgiou (University of Texas at Austin) will present a set of novel engineered Fcs for half-life extension and for highly selective engagement of a single FcγR or C1q.

The full agenda for the meeting can be found here.

Interested in attending the meeting? Society members can save 15% on the registration fee!

Not a member? Please join!

Membership is free for students and employees of the Society’s corporate sponsors.

 

Engineering and Application of Therapeutic Antibodies for Neurodegenerative Diseases

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The Antibody Society is pleased to invite you to attend its annual Meeting, Antibody Engineering & Therapeutics, which will be held December 11-15, 2017, in San Diego, CA. We will be celebrating the 10th anniversary of the Society at the Society’s Special Session on Thursday December 14, 2017.  In session previews that will be posted during September-November, the session chairs discuss the relevance of their topics to current and future antibody therapeutics development.

The nervous system is especially vulnerable to the disrupted proteostasis and accumulations of toxic forms of proteins that occur naturally with aging, and/or as a result of genetic and environmental risk factors. As our overall populations age, these disorders loom as a massive public health problem due to the level of care required for affected individuals. Antibodies, with their inherent specificity for protein isoforms, will become increasingly critical as therapeutics and diagnostics. Engineering and Application of Therapeutic Antibodies for Neurodegenerative Diseases, which will be presented on Wed. morning, Dec. 13, has been organized by Anne Messer (Neural Stem Cell Institute/ Univ. Albany), Cynthia Lemere (Brigham & Women’s Hospital/Harvard Medical School) and James Huston (Huston BioConsulting, LLC). The speakers in this session will present a range of approaches for Alzheimer’s and related dementias, Parkinson’s, and ALS/motor neuron disease, including notes on the extent to which there can be overlaps among these and other protein misfolding diseases.

The talks in the first half of the session will focus on an important target in Alzheimer’s, amyloid beta (Aβ). Isabelle Aubert (University of Toronto) will present the opening talk, “Delivery of Antibodies across the Blood-brain Barrier Using MRI-guided Focused Ultrasound,” including promising data on functional improvement after treatments with anti- Aβ antibodies. [This talk also represents a continuation of the theme of approaches to blood brain barrier permeability in the keynote talk by William Pardridge (UCLA), and a session talk by Jasi Atwal (Genentech), on Tuesday, Dec. 13.] Next in our session, Christoph Hock (University of Zurich) will present “Antibody Therapy for Alzheimer’s Disease – Key Challenges.” These challenges include targeting the most relevant Aβ species, establishing a consistent dose-response, selecting the right timing and duration of the intervention, demonstrating a clinical / biomarker correlation and managing amyloid related imaging abnormalities (ARIA E/H). 
Michael Sierks (Arizona State University) will present his cutting-edge engineering and catalytic antibody approaches to preventing formation of the toxic species in “Altering APP Processing with a Proteolytic Diabody.”

The second half of the session covers immunotherapies for multi-faceted neurodegenerations. 
Laura Ranum (University of Florida) uses a mouse model of a human mutation that can lead to motor, cognitive, and/or anxiety symptoms due to accumulation of novel mutant proteins. These may be less rare than we currently appreciate. In the talk “Towards Development of Antibody Therapy for C9orf72 ALS/FTD”, Prof. Ranum will present preclinical studies of peripheral delivery of human antibodies. 
Peter Davies (Feinstein Institute for Medical Research, NY) has developed very critical monoclonal antibodies to Tau, which is a major player in neurofibrillary tangles of Alzheimer’s disease, and the accumulating protein in hereditary and injury-induced dementias. “Treatment of Neuronal Pathology with Monoclonal Antibodies” discusses moving these valuable diagnostic and research tools into the therapeutic realm. The final talk, by Eliezer Masliah (National Institutes of Aging, NIH), is “Combinatorial Immunotherapeutic Approaches for Synucleinopathies of the Aging Population.” This innovative approach harnesses both adaptive and innate immune processes that will be critical for dealing with Parkinsons and several other aging diseases that accumulate alpha-synuclein.

Interested in attending the meeting? Society members can save 15% on the registration fee!
Not a member? Please join!
Membership is free for students and employees of the Society’s corporate sponsors.