Evidence map›Paper›PMID 26563652›Full record

ArticlemAbs2016

Development and characterization of human monoclonal antibodies that neutralize multiple TGFβ isoforms.

Daniel Bedinger, Llewelyn Lao, Shireen Khan, Steve Lee, Toshihiko Takeuchi, Amer M Mirza

Open access · goldAbstract read
In one paragraph

Article in mAbs, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
0.5field-weighted citation impact, top 33% 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

25 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
  2. Evaluation of targeted and immune combination therapies in a rat model of hormone receptor-positive breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Article
  4. Fibrosis in Immune-Mediated and Autoimmune Disorders.Journal of clinical medicine · 2025
    Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Tumor in the Crossfire: Inhibiting TGF-β to Enhance Cancer Immunotherapy.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2022
    Review
  11. Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. The Role of TGF-Evidence-based complementary and alternative medicine : eCAM · 2021
    Review
  17. TGFβ biology in cancer progression and immunotherapy.Nature reviews. Clinical oncology · 2021
    Review
  18. Article
  19. Article
  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

6 authors at 1 institution in 1 country.

Daniel Bedingera XOMA Corp. , Berkeley , 94710 , CA , USA.
Llewelyn Laoa XOMA Corp. , Berkeley , 94710 , CA , USA.
Shireen Khana XOMA Corp. , Berkeley , 94710 , CA , USA.
Steve Leea XOMA Corp. , Berkeley , 94710 , CA , USA.
Toshihiko Takeuchia XOMA Corp. , Berkeley , 94710 , CA , USA.
Amer M Mirzaa XOMA Corp. , Berkeley , 94710 , CA , USA.
XOMA (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Transforming growth factor (TGF)β levels are elevated in, and drive the progression of, numerous disease states such as advanced metastatic cancer and systemic and ocular fibrosis. There are 3 main isoforms, TGFβ1, 2, and 3. As multiple TGFβ isoforms are involved in disease processes, maximal therapeutic efficacy may require neutralization of 2 or more of the TGFβ isoforms. Fully human antibody phage display libraries were used to discover a number of antibodies that bind and neutralize various combinations of TGFβ1, 2 or 3. The primary panning did not yield any uniformly potent pan-isoform neutralizing antibodies; therefore, an antibody that displayed potent TGFβ 1, 2 inhibition, but more modest affinity versus TGFβ3, was affinity matured by shuffling with a light chain sub-library and further screening. This process yielded a high affinity pan-isoform neutralizing clone. Antibodies were analyzed and compared by binding affinity, as well as receptor and epitope competition by surface plasmon resonance methods. The antibodies were also shown to neutralize TGFβ effects in vitro in 3 assays: 1) interleukin (IL)-4 induced HT-2 cell proliferation; 2) TGFβ-mediated IL-11 release by A549 cells; and 3) decreasing SMAD2 phosphorylation in Detroit 562 cells. The antibodies' potency in these in vitro assays correlated well with their isoform-specific affinities. Furthermore, the ability of the affinity-matured clone to decrease tumor burden in a Detroit 562 xenograft study was superior to that of the parent clone. This affinity-matured antibody acts as a very potent inhibitor of all 3 main isoforms of TGFβ and may have utility for therapeutic intervention in human disease.

Indexed as

Antibodies, MonoclonalAntibodies, NeoplasmAntibodies, NeutralizingAnimalsAntibody AffinityAntibody SpecificityCell Line, TumorHumansMiceMice, NudeProtein IsoformsTransforming Growth Factor betaXenograft Model Antitumor AssaysAntibodies, MonoclonalAntibodies, NeoplasmAntibodies, NeutralizingProtein IsoformsTransforming Growth Factor betaCancerDetroit 562TGFβfibrosisphage displaySPRtumor xenograft

Identifiers

PMID26563652
PMCPMC4966579
OpenAlexW2251943031

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.