The Antibody Society

the official website of the antibody society

The Adaptive Immune Receptor Repertoire Community of The Antibody Society

You are here: Home / Archives for The Antibody Society

The Adaptive Immune Receptor Repertoire Community is now part of The Antibody Society!

by

We are pleased and proud to announce the incorporation of the Adaptive Immune Receptor Repertoire (AIRR) Community into the Society.

The AIRR Community is a research-driven group that is organizing and coordinating stakeholders in the use of next-generation sequencing (NGS) technologies to study antibody (Ab)/B-cell and T-cell receptor (TcR) repertoires. Recent advances in sequencing technology have made it possible to sample the immune repertoire in exquisite detail. AIRR sequencing has enormous promise for understanding the dynamics of the immune repertoire in vaccinology, infectious disease, autoimmunity, and cancer biology, but also poses substantial challenges. The AIRR Community was established to meet these challenges. The AIRR Community and its associated meetings and workshops are designed to develop standards and recommendations for: 1) obtaining, analyzing, curating and comparing/sharing NGS AIRR datasets; 2) using and validating tools for analyzing AIRR data; 3) relating AIRR NGS datasets to other “big data” sets, such as microarray, flow cytometric, and MiSeq gene-expression data; and 4) legal and ethical issues involving the use and sharing of AIRR data sets derived from human sources. The proceedings of the workshops, including the recommendations and action plans, will be published to benefit the larger scientific community.

To learn more about the AIRR Community and its work, please explore the items listed under the ‘AIRR Community’ tab above.

Benralizumab granted FDA approval

by

On November 14, 2017, AstraZeneca announced that benralizumab (Fasenra), an afucosylated IgG1 mab targeting the alpha subunit of IL-5R found on eosinophils, received a US Food and Drug Administration approval for the add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype. The European Medicines Agency’s Committee for Medicinal Products for Human Use adopted a positive opinion on November 10, 2017, recommending the marketing authorization of benralizumab as an add-on maintenance treatment in adult patients with severe eosinophilic asthma inadequately controlled despite high-dose inhaled corticosteroids plus long-acting b-agonists. The European Commission’s decision regarding marketing authorization in the EU is pending. Marketing applications for benralizumab are undergoing review in Japan and other countries. The mAb was in-licensed from BioWa, Inc., a wholly-owned subsidiary of Kyowa Hakko Kirin Co., Ltd. by MedImmune.

The safety and efficacy of benralizumab as a treatment for asthma were evaluated in the WINDWARD program, which included six Phase 3 trials, SIROCCO, CALIMA, ZONDA, BISE, BORA and GREGALE. The randomized, double-blinded, parallel-group, placebo-controlled SIROCCO (NCT01928771) and CALIMA (NCT01914757) trials evaluated the efficacy and safety of a regular, subcutaneous administration of a fixed 30 mg dose of benralizumab for up to 56 weeks in exacerbation-prone adult and adolescent patients 12 years of age and older. Study results were published in 2016. [1, 2] In the 28-week randomized ZONDA study (NCT02075255), the effects of 30 mg benralizumab administered subcutaneously either every 4 weeks or every 8 weeks (with the first three doses administered every 4 weeks) versus placebo on the reduction in the oral glucocorticoid dose while asthma control was maintained in adult patients with severe asthma. The study’s primary outcome measure, percentage reduction in final oral steroid dose compared with baseline while maintaining asthma control, was met. The median final oral glucocorticoid doses from baseline were reduced by 75% in patients who received either dose of benralizumab,  compared with a reduction of 25% in the oral glucocorticoid doses in the placebo group (P<0.001 for both comparisons). [3]

  1. Bleecker ER, FitzGerald JM, Chanez P, Papi A, Weinstein SF, Barker P, Sproule S, Gilmartin G, Aurivillius M, Werkström V, et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet 2016; pii: S0140-6736(16)31324-1. doi: 10.1016/S0140-6736(16)31324-1.
  2. FitzGerald JM, Bleecker ER, Nair P, Korn S, Ohta K, Lommatzsch M, Ferguson GT, Busse WW, Barker P, Sproule S, et al. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016; pii: S0140-6736(16)31322-8. doi: 10.1016/S0140-6736(16)31322-8.
  3. Nair P, Wenzel S, Rabe KF, Bourdin A, Lugogo NL, Kuna P, Barker P, Sproule S, Ponnarambil S, Goldman M; ZONDA Trial Investigators. Oral Glucocorticoid-Sparing Effect of Benralizumab in Severe Asthma. N Engl J Med. 2017;376(25):2448-2458. doi: 10.1056/NEJMoa1703501.

The Antibody Society maintains a comprehensive table of approved antibody therapeutics and those in regulatory review in the EU or US. As of November 15, 2017, a total of 9 mAbs have been granted first approvals in either the US or EU in 2017, and marketing applications for a total of 10 antibody therapeutics that have not yet been approved in either the EU or US are undergoing review in these regions.

Please log in to access the table, located in the Members Only section.

Not a member? Please join! Membership is free for students and employees of the Society’s corporate sponsors.

Mogamulizumab enters EU regulatory review

by

Mogamulizumab (KW-0761, Poteligeo®), is an IgG1 afucosylated humanized monoclonal antibody targeting CC chemokine receptor 4 (CCR4) expressed on tumor cells of patients with cutaneous T-cell leukemia lymphoma (CTCL), including mycosis fungoides and Sézary syndrome. Afucosylation enhances the antibody-dependent cell-mediated cytotoxicity (ADCC) activity of the mAb. Mogamulizumab was initially approved in Japan in March 2012 for the treatment of patients with relapsed or refractory CCR4-positive adult T-cell leukemia-lymphoma (ATL), and then granted marketing authorization in Japan for the treatment of patients with relapsed or refractory CCR4-positive, peripheral T-cell lymphoma (PTCL) and CTCL in March 2014, and with chemotherapy-naive CCR4-positive ATL in December 2014.

In October 2017, Kyowa Hakko Kirin announced that a marketing authorization application (MAA) for mogamulizumab, for the treatment of CTCL in adults who have received at least one prior systemic therapy, is under review at the European Medicines Agency. The MAA includes data from the randomized, open-label, multi-center Phase 3 MAVORIC study (NCT01728805), which evaluated the effects of mogamulizumab versus vorinostat (Zolinza®) in patients with refractory cutaneous T cell lymphoma who failed previous treatment. The study included 372 patients who were randomized to receive either mogamulizumab (1.0 mg/kg weekly x 4 in cycle 1, then every other week until progression) or vorinostat (400 mg orally daily). The primary outcome measure of the study was progression-free survival (PFS), with the target being a 50% improvement over the reference median PFS for vorinostat (median PFS of 254 days for the mogamulizumab arm versus 169 days for the vorinostat arm). In April 2017, Kyowa Hakko Kirin announced top-line results from the MAVORIC study indicating the primary endpoint of PFS had been met. In August 2017, mogamulizumab received breakthrough therapy designation in the US for mycosis fungoides and Sézary syndrome based on results from the MAVORIC study.

The Antibody Society maintains a comprehensive table of approved antibody therapeutics and those in regulatory review in the EU or US. As of November 10, 2017, marketing applications for a total of 11 antibody therapeutics that have not yet been approved in either the EU or US are undergoing review in these regions.

Please log in to access the table, located in the Members Only section.

Not a member? Please join!

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

Post-translational Modification in Antibody Function

by

The Antibody Society is pleased to invite you to attend its annual Meeting, Antibody Engineering & Therapeutics, which will be held December 12-15, 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 this session summary, Dennis R. Burton (The Scripps Research Institute) and Paul W.H.I. Parren (Leiden University Medical Center) discuss what you will learn in their session on post-translational modification in antibody function.

The critical importance of sequence variation in antibodies is well recognized. Sequence diversity in antibody variable domains is essential for specific antigen recognition while linkage to different constant domains leads to distinct Fc-mediated effector activities. Post-translational modifications (PTMs) of these domains provide an additional immune mechanism by which the binding and activity of antibodies can be modulated. PTMs vary from chain additions, such as N- and O-linked glycosylation, glycation, cysteinylation and sulfation; chain trimming, such as C-terminal lysine clipping; amino acid modifications such as cyclization (into a N-terminal pyroglutamic acid), deamidation, oxidation, isomerization and carbamylation; to disulfide scrambling of hinge region interchain disulfide bonds. Each antibody can therefore give rise to a myriad of distinct antibody molecules with large activity and potency differences. Although post-translational modifications of antibodies have been observed and studied for decades, we only now start to understand the full impact of this incredible microheterogeneity. PTMs have moved from being viewed as a mere nuisance to antibody manufacturing that requires controlling to a potential handle to modify and improve specific antibody functions.

In this session, we will hear about current state-of-the-art in PTM detection and novel insights into the role and modulation of PTMs in our immune system as well as the way in which we can exploit PTMs to make better (therapeutic) antibodies. The first and the second (after the break) part of our session will be initiated with lectures by renowned experts in their fields. Professor Albert Heck (Utrecht University) is a world-expert on the structural analysis of proteins by mass spectrometry. He received the Frank H. Field and Joe L. Franklin Award for outstanding achievement in mass spectrometry from the American Chemical Society and in 2017 he was received the NWO Spinoza Prize, which is the highest award in Dutch Science. Prof Heck will discuss how innovative and advanced mass spectrometry methods can be used to map antibody heterogeneity due to PTMs. Leendert Trouw (Leiden University Medical Center) will discuss the role of two amino acid modifications (citrullination and carbamylation) in the autoimmune disease rheumatoid arthritis (RA). On the one hand, the presence of antibodies against citrullinated or carbamylated proteins represents a prognostic marker for the disease. How antibodies recognize diverse antigens carrying these modifications is therefore an important area of study. Carbamylation of antibodies furthermore may also have functional consequences for antibody effector functions which will be highlighted. Professor Gerhard Krönke (University of Erlangen) will discuss how the PTM profile and inflammatory activity of autoantibodies in RA is regulated by TH17 helper T cells. His work gives us a novel insight into a mechanism by which the cellular immune system regulates the activity of antibodies and how its derailment may lead to the initiation of (autoimmune) disease.

After the break, Taia Wang (Stanford University School of Medicine) will discuss the diverse downstream proinflammatory, anti-inflammatory and immunomodulatory consequences of the engagement of type I and type II Fc receptors, which are influenced by the Fc’s amino acid sequence and the complex, biantennary Fc-associated N-linked glycan, in the context of infectious, autoimmune, and neoplastic disorders. Yingda Xu (Adimab) will bring us back to the importance of PTMS in manufacturing and control of therapeutic antibody production. He will show novel data on the identification of chemically labile sites in antibodies and how this information may be used in therapeutic antibody lead selection. Finally, Raiees Andrabi (The Scripps Research Institute) will discuss how sulfation of residues in the antibody binding site is critical for certain broadly neutralizing anti-HIV-1 antibodies targeting the envelope glycoprotein.

We hope that this session will convey the current interest and high excitement in antibody PTMs and will serve to promote further research into the importance and impact of PTM microheterogeneity for polyclonal antibody responses as well as for monoclonal antibody therapeutics.

 

Interested in attending the meeting? Learn more from this PDF, which includes all session summaries written by the chairpersons.

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.

 

 

Novel antibody display, selection and screening technologies

by

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!

The session on “Novel antibody display, selection and screening technologies”, chaired by Andrew Bradbury, M.D., Ph.D. Research Scientist and Group Leader, Los Alamos National Laboratories; Chief Scientific Officer, Specifica, focusses on the new technologies expected to advance antibody library generation and selection in the future. Many of these reflect the rapidly growing role of next generation sequencing (NGS) in all aspects of in vitro antibody generation. Dr. Bradbury will discuss how NGS has enabled more informed discussions on antibody library sizes, and how traditional selection from antibody libraries does not address the full depth of possible positive antibodies. Tim Whitehead (Michigan State University) will discuss the power of NGS in protein engineering to analyze the outcomes of different selective pressures on antibody stability, affinity and function, and to use this information in antibody discovery programs, while Brandon DeKosky (The University of Kansas) will describe how the combination of cloning natural paired antibody responses to viruses with yeast display vectors provides insights into neutralizing HIV and Ebola responses. In addition to NGS, Benjamin Hackel (University of Minnesota) will describe the engineering of novel alternative novel yeast display vectors as applied to the development of novel small non-antibody scaffolds. James Wells (UCSF) will describe an innovative use of novel proteomic technologies involving phage display to both understand how cancer cells remodel their membrane proteomes, as well as to generate recombinant antibodies against them. Once potential therapeutic antibody leads have been identified, they need to be further developed before they can be used in the clinic. This involves understanding and overcoming fundamental challenges related to the design and selection of antibodies with high affinity, specificity, stability and solubility, a topic that will addressed by Peter Tessier (University of Michigan).

Interested in attending the meeting? Learn more from this PDF, which includes all session summaries written by the chairpersons.

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.