Evidence map›Paper›PMID 40237925›Full record

ReviewBioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy2025

Understanding IgM Structure and Biology to Engineer New Antibody Therapeutics.

Johannes Buchner, Roberto Sitia, Hristo L Svilenov

Abstract readReview
In one paragraph

Review in BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed.

  1. Trial
  2. IgM promotes antitumor immunity to a Tn-expressing solid tumor.Journal for immunotherapy of cancer · 2026
    Article
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  5. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors.

Johannes BuchnerDepartment Bioscience, Center for Protein Assemblies, School of Natural Sciences, Technical University of Munich, Ernst-Otto-Fischer-Strasse 8, 85748, Garching, Germany.
Roberto SitiaDivision of Genetics and Cell Biology, Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Via Olgettina 58, Milan, Italy.
Hristo L SvilenovBiopharmaceutical Technology, TUM School of Life Sciences, Technical University of Munich, Emil-Erlenmeyer-Forum 5, 85354, Freising, Germany. hristo.svilenov@tum.de.ORCID http://orcid.org/0000-0001-5863-9569

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Immunoglobulin M (IgM) antibodies are an essential and conserved part of adaptive immunity. IgMs assemble into pentamers and hexamers that bind to antigens with high avidity. Pentamers incorporate a small protein called J-chain (JC) that is important for their transcytosis via the poly-immunoglobulin receptor (pIgR). IgM antibodies can efficiently activate complement and interact with different Fc receptors (FcμR, Fcα/μR, pIgR) that trigger distinct effector functions and biodistribution. Even if these features have made the clinical use of IgM attractive over the past decades, there are currently no approved therapeutic IgMs on the market. In this review, we summarize the recent advances in the knowledge of IgM biogenesis and structure and discuss the therapeutic opportunities of IgM over IgG arising from high avidity, target clustering, binding to distinct IgM receptors, complement activation, transcytosis, and protein engineering opportunities. In addition, we summarize possibilities and outstanding challenges in the production of therapeutic IgM, including available technologies for IgM purification. Finally, we review recent preclinical and clinical data showing that IgM outperforms IgG in various in vitro assays but still fails to pass through clinical trials successfully. Challenges remain for IgM development, such as the need for a better understanding of IgM biology to facilitate a smoother transition from the preclinic to successful clinical trials.

Indexed as

Immunoglobulin MProtein EngineeringAnimalsComplement ActivationHumansReceptors, FcImmunoglobulin MReceptors, Fc

Identifiers

PMID40237925
PMCPMC12031937

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.