Evidence map›Paper›PMID 28323513›Full record

ArticlemAbs

Transmembrane TNF-dependent uptake of anti-TNF antibodies.

Arun Deora, Subramanya Hegde, Jacqueline Lee, Chee-Ho Choi, Qing Chang, Cheryl Lee, Lucia Eaton, Hua Tang, Dongdong Wang, David Lee and 8 more

Open access · goldAbstract read
In one paragraph

Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
2.9field-weighted citation impact, top 9% of its field
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

43 citing papers in PubMed, 78 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Pharmacogenomics of TNF inhibitors.Frontiers in immunology · 2025
    Review
  10. Article
  11. Reducing Immunogenicity by Design: Approaches to Minimize Immunogenicity of Monoclonal Antibodies.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024
    Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article
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

18 authors at 1 institution in 1 country.

Arun Deoraa AbbVie Bioresearch Center , Worcester , MA , USA.
Subramanya Hegdea AbbVie Bioresearch Center , Worcester , MA , USA.
Jacqueline Leea AbbVie Bioresearch Center , Worcester , MA , USA.
Chee-Ho Choia AbbVie Bioresearch Center , Worcester , MA , USA.
Qing Changa AbbVie Bioresearch Center , Worcester , MA , USA.
Cheryl Leea AbbVie Bioresearch Center , Worcester , MA , USA.
Lucia Eatona AbbVie Bioresearch Center , Worcester , MA , USA.
Hua Tangb AbbVie Inc , North Chicago , IL , USA.
Dongdong Wanga AbbVie Bioresearch Center , Worcester , MA , USA.
David Leea AbbVie Bioresearch Center , Worcester , MA , USA.
Mark Michalaka AbbVie Bioresearch Center , Worcester , MA , USA.
Medha Tomlinsona AbbVie Bioresearch Center , Worcester , MA , USA.
Qingfeng Taoa AbbVie Bioresearch Center , Worcester , MA , USA.
Nidhi Gaura AbbVie Bioresearch Center , Worcester , MA , USA.
Bohdan Harveya AbbVie Bioresearch Center , Worcester , MA , USA.
Shaun McLoughlinb AbbVie Inc , North Chicago , IL , USA.
Boris Labkovskya AbbVie Bioresearch Center , Worcester , MA , USA.
Tariq Ghayura AbbVie Bioresearch Center , Worcester , MA , USA.
AbbVie (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

TNF-α (TNF), a pro-inflammatory cytokine is synthesized as a 26 kDa protein, anchors in the plasma membrane as transmembrane TNF (TmTNF), and is subjected to proteolysis by the TNF-α converting enzyme (TACE) to release the 15 kDa form of soluble TNF (sTNF). TmTNF and sTNF interact with 2 distinct receptors, TNF-R1 (p55) and TNF-R2 (p75), to mediate the multiple biologic effects of TNF described to date. Several anti-TNF biologics that bind to both forms of TNF and block their interactions with the TNF receptors are now approved for the treatment of a variety of immune-mediated diseases. Several reports suggest that binding of anti-TNFs to TmTNF delivers an outside-to-inside 'reverse' signal that may also contribute to the efficacy of anti-TNFs. Some patients, however, develop anti-TNF drug antibody responses (ADA or immunogenicity). Here, we demonstrate biochemically that TmTNF is transiently expressed on the surface of lipopolysaccharide-stimulated primary human monocytes, macrophages, and monocyte-derived dendritic cells (DCs) and expression of TmTNF on the cell surface is enhanced following treatment of cells with TAPI-2, a TACE inhibitor. Importantly, binding of anti-TNFs to TmTNF on DCs results in rapid internalization of the anti-TNF/TmTNF complex first into early endosomes and then lysosomes. The internalized anti-TNF is processed and anti-TNF peptides can be eluted from the surface of DCs. Finally, tetanus toxin peptides fused to anti-TNFs are presented by DCs to initiate T cell recall proliferation response. Collectively, these observations may provide new insights into understanding the biology of TmTNF, mode of action of anti-TNFs, biology of ADA response to anti-TNFs, and may help with the design of the next generation of anti-TNFs.

Indexed as

AntibodiesAnimalsCell MembraneDendritic CellsHEK293 CellsHumansMacrophagesMiceMonocytesReceptors, Tumor Necrosis Factor, Type IReceptors, Tumor Necrosis Factor, Type IITumor Necrosis Factor-alphaAntibodiesReceptors, Tumor Necrosis Factor, Type IReceptors, Tumor Necrosis Factor, Type IITumor Necrosis Factor-alphaAnti-drug antibodies (ADA)anti-TNFsclathrinendocytosismembrane TNFtetanus toxinTmTNF reverse signalingTransmembrane TNF

Identifiers

PMID28323513
PMCPMC5419086
OpenAlexW2600926306

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.