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Call for papers: Attention Society members who are also authors!

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mAbs is the official journal of The Antibody Society. Each year, the journal’s publisher, Taylor & Francis, provides several article publishing charge (APC) waivers, with a value of up to $4000 USD / £3200 / €3840 / $5570 AUD each, that we may distribute to members. To be considered for an APC waiver, please submit pre-submission inquiries, which should include the authors, title, abstract, and general outline of the intended article, to membership@antibodysociety.org.

mAbs publishes high quality reports, reviews, and perspective articles covering a range of antibody R&D topics, including:

  • Design, engineering, and selection of antibody therapeutics, including antibody-drug conjugates, multispecific antibodies, and single-domain antibodies
  • Machine learning and artificial intelligence applications
  • Non-clinical studies of antibodies, such as mechanism of action studies, safety, and efficacy studies in animals
  • Manufacturing and formulation
  • Regulatory review and approval of antibody therapeutics

The deadline for submission of the APC waiver request is July 31, 2023.

The deadline for submission of the manuscript to the journal is January 31, 2024.

The selected recipients will be notified as soon as possible after the request submission deadline.

Please contact Janice Reichert (janice.reichert@antibodysociety.org) if you have questions.

Further information:

mAbs is a multidisciplinary, open access journal dedicated to the art and science of antibody research and development. The journal has a strong scientific and medical focus but serves a broad readership, including specialists in technology transfer, legal issues, investment, and the regulation of therapeutics.

The journal’s 2021 Impact Factor is 6.440 and, in total, articles are downloaded at a rate of over 1 million per year.

Members of The Antibody Society receive a 10% discount on article publication charges using their member code.

FDA approves bispecific antibody EPKINLY™ (epcoritamab-bysp)

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On May 19, 2023, the US Food and Drug Administration approved EPKINLY™ (epcoritamab-bysp) for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B‑cell lymphoma, after two or more lines of systemic therapy. Created using Genmab’s DuoBody® technology, epcoritamab (GEN3013, DuoBody®-CD3xCD20) is a T cell-engaging bispecific IgG1k/l antibody targeting CD20 and CD3 that is jointly owned by Genmab and AbbVie. EPKINLY was approved under FDA’s accelerated approval program based on response rate and durability of response. Continued approval for this indication is contingent upon verification and description of clinical benefit in a confirmatory trial(s).

FDA’s approval was supported by data from the pivotal Phase 1/2 EPCORE NHL-1 trial (NCT03625037) studying epcoritamab in 157 patients with relapsed or refractory large B-cell lymphoma who had received at least two prior systemic therapies, including some who had received prior treatments with CAR-T cell therapy. The dose escalation findings from the Phase 1 part identified a dose of 48 mg as the recommended Phase 2 dose. In the Phase 2 part, patients received 48 mg of epcoritamab as 1 ml subcutaneous injections in 28-day cycles, with weekly dosing in Cycles 1-2, dosing every second week in Cycles 3-6, and dosing every 4 weeks from Cycle 7 onward. An overall response (complete or partial response) was seen in 61% (90/148 [95 percent confidence interval (CI): 52.5-68.7]) of patients and 38% (56/148 [95 percent CI: 30.0-46.2]) achieved complete remission. The median duration of response was 15.6 months (95 percent CI: 9.7-Not reached).

Epcoritamab is being investigated in multiple ongoing clinical studies across different settings and histologies. The most advanced of these is the randomized, open-label Phase 3 EPCORE™DLBCL-1 trial (NCT04628494) of epcoritamab vs investigator’s choice chemotherapy in patients with R/R DLBCL. The study is recruiting an estimated 552 patients and has an estimated primary completion date in June 2024.

Interested in data for other antibody therapeutics that have received marketing authorizations? Go to our searchable table of approved antibody therapeutics and those in regulatory review for more information.

First global approval for glofitamab (COLUMVI®)

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Hoffmann-La Roche Limited (Roche Canada) announced that on March 24, 2023 Health Canada authorized COLUMVI® (glofitamab for injection) for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from follicular lymphoma (trFL), or primary mediastinal B-cell lymphoma (PMBCL), who have received two or more lines of systemic therapy and are ineligible to receive or cannot receive CAR-T cell therapy or have previously received CAR-T cell therapy. COLUMVI has been issued marketing authorization with conditions, pending the results of trials to verify its clinical benefit. The authorization of COLUMVI® is the first in Canada and globally.

Glofitamab (RO7082859) is a full-length IgG1λ/ҡ bispecific T cell redirecting antibody targeting CD20 on malignant B cells and CD3 on T cells. This bispecific antibody was developed by Roche using the 2:1 CrossMab technology, characterized by 3 antigen-binding fragment (Fab) arms enabling monovalent binding to CD3ɛ and bivalent binding to CD20, with the second CD20 arm fused to the CD3ɛ-binding arms via a flexible linker. Glofitamab also features a heterodimeric Fc region engineered with PG LALA mutations to abolish binding to FcɣRs and C1q.

The Health Canada authorization is based on data from the open-label, phase I/II, multicenter, multi-cohort trial (NP30179) conducted to evaluate COLUMVI as monotherapy in patients with relapsed or refractory B-cell lymphoma. In the single-arm DLBCL cohort (n=108), 84.3% of patients were refractory to their most recent therapy and about one-third (34.3%) had received prior CAR T-cell therapy. The primary efficacy outcome measure was complete response (CR) rate as assessed by the IRC using 2014 Lugano response criteria. Results showed that 35.2% of patients (n=38/108) achieved a complete response (CR; a disappearance of all signs of cancer), and 50.0% (n=54/108) achieved an objective response (OR; the combination of CR or partial response, a decrease in the amount of cancer in their body).

An marketing authorization application containing data from the Phase 1/2 NP30179 study (NCT03075696) evaluating glofitamab for NHL was submitted to the European Medicines Agency. A biologics license application for glofitamab undergoing review by the Food and Drug Administration has a first action date of July 1, 2023.

Need data for other antibody therapeutics that have received marketing authorizations? Go to our searchable table of approved antibody therapeutics and those in regulatory review for more information.

Efgartigimod: A Novel FcRn Antagonist in the Treatment of Autoimmune Diseases

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Summary written by Alicia Chenoweth, PhD, King’s College London

Antibody Engineering & Therapeutics, held in December 2022, offered many opportunities to hear exciting and informative presentations by experts in the field, including Dr. Hans de Haard, Chief Scientific Officer at argenx.

Dr. de Haard’s talk, Efgartigimod: A Novel FcRn Antagonist in the Treatment of Autoimmune Diseases, detailed the mechanism of action and clinical trial results of the FcRn antagonist efgartigimod. Efgartigimod is a human IgG1 Fc fragment with five “Abdeg” mutations (M252Y, S254T, T256E, H433K, N434F) to increase its affinity for FcRn at both low pH and neutral pH (1,2). It is designed to outcompete the binding of serum IgG for FcRn, leading to degradation of the unbound IgG and recycling of efgartigimod back to the surface of the cell to be released back into circulation.

Dr. de Haard discussed the findings of a recent publication in which the biochemical, structural, and in vivo properties of efgartigimod and a full-length antibody counterpart containing the same Abdeg mutations were compared (3). Crystallographic studies of FcRn in complex with the full-length antibody demonstrated that the antigen-binding fragment projects towards the membrane, leading to a potential steric clash hindering binding. This hypothesis was confirmed using a bioassay measuring receptor occupancy, showing that efgartigimod gave a better FcRn occupancy and had improved uptake compared to the full-length antibody. Furthermore, in cynomolgus monkeys, the Fc fragment gave a much faster clearance of tracer antibody and a more potent pharmacodynamic effect compared to full-length antibody. Thus, the Fc fragment was determined to be the better performing FcRn antagonist over the full-length antibody due to improved blocking of IgG recycling in vitro and the more potent PD effect in vivo.

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Engineering of human sialidase Neu2 as novel immunotherapy

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Post written by Czeslaw Radziejewski, Ph.D.

Antibody Engineering & Therapeutics, held in December 2022, offered many opportunities to hear exciting and informative presentations by experts in the field, including Li Peng, Ph.D., who discussed “Engineering of human Sialidase Neu2 as Novel Immunotherapy for Degrading Immunosuppressive Sialoglycans to Enhance Antitumor T-Cell Immunity”.

Glycans are the most abundant structures on the cell surface. They are involved in cell communication with immune cells, and abnormal glycans can cause immune dysfunction in cancer and inflammatory diseases. Glycans typically terminate in sialic acid, but in cancer cells, sialic acid is present at a much higher abundance. The most common sialic acid in humans is N-acetylneuraminic acid, which plays a crucial role in numerous intercellular interactions, including with immune cells in the extracellular matrix, epithelial cells, and antibodies. Many studies have shown that sialoglycans are immunosuppressive and that high levels of surface sialoglycans are linked with poor outcomes in many tumor types. Hypersialylation of the surface of cancer cells makes these cells prime ligands for sialic acid-binding immunoglobulin-type lectins (Siglecs), which are found on the surface of immune cells. Once bound to sialylated glycans, Siglecs promote immunosuppressive signaling, thus conferring protection on the tumor cell. There are 15 human Siglecs. In addition, CD-28 is also known to bind sialoglycans. Most immune cells express more than one Siglec.

In her plenary lecture at the 2022 Antibody Engineering & Therapeutics conference, Professor Carolyn Bertozzi, outlined opportunities for the development of cancer treatments based on understanding the cell-surface glycome. She favored degrading sialoglycans with the enzyme sialidase to eliminate the immunosuppression promoted by Siglecs. As proof of concept, a fusion protein was created in Bertozzi’s lab using click chemistry, linking bacterial sialidase to the C-terminus of trastuzumab. The conjugate was tested in a mouse model of a trastuzumab-resistant HER2+ breast cancer model, and the results showed that the treatment essentially abrogated tumor growth. Based on these promising findings, Bertozzi cofounded Palleon Pharmaceuticals to explore sialidase-based biotherapies for cancer treatment.

At the conference, Dr. Li Peng, Chief Scientific Officer of Palleon Pharmaceuticals, presented the company’s progress in moving this concept toward the clinic. Palleon created a set of proprietary Siglec-based reagents for immunohistological hypersialylation detection and probing its role in immunotherapy resistance. Using such reagents, Palleon examined tissues from metastatic melanoma patients treated with PD1 blockade and showed that patients with a high level of sialylation fared much worse than patients with lower levels of sialoglycans. Following Bertozzi’s line of reasoning, the company pursued a strategy of using the enzymatic functionality of sialidase to remove excessive cell-surface sialylation. To translate this idea into a human therapeutic, Palleon decided to use a genetic fusion of sialidase with human Fc.

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