Talk:WikiJournal Preprints/MALT1
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This article is an unpublished pre-print undergoing public peer review organised by the WikiJournal of Science.
It is adapted from the Wikipedia page MALT1. It contains some or all of that page's content licensed under a Creative Commons Attribution ShareAlike License and will also be used to update that article after peer review.You can follow its progress through the peer review process at this tracking page.First submitted:
Article text
QID: Q116768205
Suggested (provisional) preprint citation format:
Jens Staal. "MALT1". WikiJournal Preprints. Wikidata Q116768205.
License: 
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction, provided the original author and source are credited.
Henry Hoff 
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Lara Heller
Achim Schlapbach
Article information
This is the pre-publication public peer review for the article MALT1
Plagiarism check
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Pass. Report from WMF copyvios tool flagged the protein's full name (Mucosa-associated lymphoid tissue lymphoma translocation protein 1) as identical to other websites, which is not a concern. OhanaUnitedTalk page 17:11, 15 May 2023 (UTC)
Editorial comments
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Comments by Andrew Leung 
,
These editorial comments were submitted on , and refer to this previous version of the article
Before sending the manuscript out for peer review, I would like to see the following points to be improved:
- It should provide a brief history on how the protein was discovered (and by whom).
- It is unclear to the readers what MALT1's interactions with other proteins are about. Do the interactions activate or inhibit other activities?
- The bullet-point sentences in "Protease inhibitors" section currently looks like a "laundry list of items". They should be organized into paragraphs based on commons themes.
You may draw from WikiJournal of Science/RIG-I like receptors and WikiJournal of Science/The TIM barrel fold as examples of the type of detail and layout of a manuscript on proteins.
OhanaUnitedTalk page 17:21, 15 May 2023 (UTC)
Comments by Guy Vandegrift ,
These editorial comments were submitted on , and refer to this previous version of the article
I did a search for [[w:MALT1 and [[wikipedia:MALT1 and found nothing. Is there a policy reason why no link to w:MALT1 exists in this article?
Guy vandegrift (discuss • contribs) 23:34, 23 April 2024 (UTC)
- In the infobox to the right, the article states that "It is adapted from the Wikipedia page w:MALT1." OhanaUnitedTalk page 13:47, 2 July 2024 (UTC)
Peer Review 1
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reviewer-annotated pdf
Review by Lara Heller née Hartjes , Zentrum für Humangenetik Tübingen
These assessment comments were submitted on , and refer to this previous version of the article
Very nice overview article on MALT1 with the most important functions and information covered. I only had some small suggestions where one could add information or summarize. I especially liked the list of MALT1 inhibitors and pharmaceutical companies working on them, since this is information not as easily found in other sources. Please find my other comments and small corrections in the attached PDF file.
OhanaUnitedTalk page 13:51, 2 July 2024 (UTC)
- Comment 1: mTOR signaling: Good suggestion! I will add this to the intro
- Histidine 414 : This should indeed be Histidine 415. A typo
- Agree with the suggested changes for the role of BCL10 cleavage. This part of the text is old. The same thing for the role of the A20 cleavage. At the time that text was written, those were the only known substrates.
- Solid cancers for sure an important addition. I would here also add enhancement of immune check point inhibition (Treg depletion, possibly differentiation of TAMs from M2 to M1, enhanced IFNg producing T cells...)
- I agree with the added sentence about the importance of MALT1 scaffold function for NF-kappaB activation
- Will remove "different" from "several different"
- I will check if I can fix the reference to one of the clinical trials.
- Thank you so much for your very valuable feedback. Staalmannen (discuss • contribs) 06:37, 23 October 2024 (UTC)
Peer review 2
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Review by anonymous peer reviewer , Researcher in internal medicine and vascular medicine
These assessment comments were submitted on , and refer to this previous version of the article
The page provides an overview of the MALT1 protein. The Protease inhibitors section could benefit from an updated assessment of the current state of clinical trials and the challenges faced in developing effective MALT1 inhibitors. Further, addressing ongoing research efforts and potential future directions would provide a more forward-looking perspective.
Additional clinical trials to be included:
- A Study to Investigate the Safety, Tolerability, PK, PD, and Efficacy of ONO-7018 in Patients With R/R NHL or CLL (ClinicalTrials.gov ID: NCT05515406)
- Study of SGR-1505 in Mature B-Cell Neoplasms (ClinicalTrials.gov ID: NCT05544019)
- Study of MPT-0118 in Subjects With Advanced or Metastatic Refractory Solid Tumors (ClinicalTrials.gov ID: NCT04859777)
- A Study of the MALT1 Inhibitor JNJ-67856633 and Ibrutinib in Combination in B-cell NHL and CLL (ClinicalTrials.gov ID: NCT04876092)
OhanaUnitedTalk page 19:45, 3 September 2024 (UTC)
- Thank you. I will add the additional clinical trials to the article.
- The risk with "future perspectives" is that this of course will be biased by my own research interests. I think we will see more work being done on the role of MALT1 protease activity in non-lymphocyte cells - in innate immune cells downstream of CARD9, and in non-hematopoetic cells downstream of CARD10 and CARD14.
- A BIG and still unanswered question is which substrate that is responsible for the autoimmune phenotype we see in MALT1 protease-dead knock-in mice. Knowing this, we might be able to undo the harmful side effects of MALT1 protease inhibition. Staalmannen (discuss • contribs) 06:43, 23 October 2024 (UTC)
- Another big-ish and unanswered question that I think would be interesting to investigate is whether JAK inhibitors could eliminate the negative side effects from MALT1 protease inhibition (by blocking the effects of IFNg). MALT1/JAK dual inhibitor mixes could be quite interesting therapeutically in some cases. Staalmannen (discuss • contribs) 15:13, 30 October 2024 (UTC)
Peer review 3
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Review by Achim Schlapbach ,
These assessment comments were submitted on , and refer to this previous version of the article
Overall, a Wiki review on MALT and the progress in the field is very welcome. Below are a few remarks for consideration or amendment:
Generally, paracaspase should be replaced by MALT1, or MALT1 paracaspase
3rd paragraph: Sequence analysis shows (not proposes)
As the field progressed significantly, several additions and amendments should be made:
Pharmacological inhibition, similar to genetic ablation of the protease activity has show an autoimmune phenotype, which put MALT1 as a drug target into question:
Recently, it has been shown that MALT1 deficiency in humans causes CID (Ref: McKinnon, M.L. et al. (2014) J. Allergy Clin. Immunol. 133, 1458–1462, Jabara, H.H. et al. (2013) J. Allergy Clin. Immunol. 132, 151–158, Punwani, D. et al. (2015) J. Clin. Immunol. 35, 135–146), furthermore protease dead knock-out mice show an autoimmune phenotype. Similar findings were made using pharmacological inhibition. (Refs: Bornancin, F. et al. J. Immunol. 194, 3723–3734, (2015), Gewies, A. et al. Cell Rep. 9, 1292–1305 (2014), Yu, J.W. et al. PLoS ONE 10, e0127083 (2015), Jaworski, M. et al., EMBO J. 33, 2765–2781 (2014), K. Martin et.al. Frontier in Immunology, 11, 2020, https://doi.org/10.3389/fimmu.2020.00745
For a review on the dual role of MALT1, see: A. Demeyer, J. Staal, R. Beyaert, TiMM, 22, 135 (2016)
The “Protease Inhibitor” section needs some amendments. All LMW inhibitors should listed or cited (possibly grouped by MoA).
Active site: VRPR-fmk, Rebeaud, et.al. Nat Immunol. 9, 272-281 (2008) (ref.8), MI-2
Allosteric: Phenothiazines, Janssen, Novartis, Lupin/AbbVie, AZ
Nat. products: Lapachone, secondary fungal metabolites
others/unknown MoA: VIB/Galapagos
Many references need to be added or amended:
Omit the Chordia reference (41) as it is not retrievable anymore
Janssen Ref: Abstract 5690: Discovery of JNJ-67856633: A novel, first-in-class MALT1 protease inhibitor for the treatment of B cell lymphomas, Cancer Res (2020) 80 (16_Supplement): 5690 https://doi.org/10.1158/1538-7445.AM2020-5690
A section: compounds in advanced preclinical or clinical studies could be added or (even better) joined to the protease inhibitor section:
Excientia: EXS73565 Ph1/2
Schrödinger: SGR-1505 Ph1
Lupin: Ph1
Exelixis: XL114 Ph1 (Aug 2022)
Rheos: RHX-317 Ph1 (July2022)
Monopteros: MPT-0118 Preclinical (Apr2022)
Rheos/Medivir: Joined patent (Oct2021)
Chordia/Ono: Licence on CTX-177 (Dec2020)
Lupin/AbbVie: Licence to Lupin MALT1 (Dec2018)
VIB/CD3/Galapagos: Partnership on MALT1 (Jan2018)
VIB/CD3: Licence agreement to AZ (Jan2014)
- Thank you. Indeed some parts are outdated by now and will be updated. Thank you for your valuable input. I will for sure integrate it. Also important will be to add a section with the CID from MALT1 loss in patients and the immune phenotypes in mice lacking protease activity (protease-dead knock-in mice) and scaffold activity (TRAF6 binding mutants)
- It is a good idea to split up the inhibitors based on mode of action (active site vs allosteric vs natural product). I will also try to do that. Staalmannen (discuss • contribs) 06:49, 23 October 2024 (UTC)