Ustekinumab neutralizes human IL‐12 and IL‐23 mediated Th1 and Th17 cell function and provides clinical benefit to patients with plaque psoriasis
Bibliographic record
Abstract
Ustekinumab (aka CNTO 1275) is a fully human IgG1k monoclonal antibody that specifically binds to human and non‐human primate IL‐12/23p40, the 40 kDa protein subunit of the heterodimeric cytokines IL 12 and IL 23. The precise molecular interactions between ustekinumab and IL‐12/23p40 are well characterized through crystal structure, protein mutagenesis, and stoichiometry analysis. Ustekinumab demonstrates equivalent neutralization of IL‐12 and IL‐23 bioactivity by binding to IL‐12/23p40 and preventing interaction with the cell surface IL‐12Rb1 receptor protein. Ustekinumab does not bind to receptor bound IL‐12 or IL‐23 and does not stimulate complement dependent cytotoxicity. In addition, equivalent neutralization is achieved with intact IgG or Fab fragments of ustekinumab. Thus, there is no evidence that the Fc component of ustekinumab contributes to the mechanism of action. Ustekinumab effectively neutralizes all human IL‐12 (Th1) and IL‐23 (Th17) mediated cellular responses tested using in vitro bioassays. Th1 and Th17 cascades are associated with a variety of human immune‐mediated diseases. Thus, ustekinumab may serve as a first‐in‐class therapy with broad applications in areas of unmet medical need. Indeed, ustekinumab provides a significant level of efficacy in the majority of subjects in clinical studies of plaque psoriasis. (All funding was provided by Centocor R&D)
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".