Human MAdCAM-1 antibodies as targeted immune modulators
Bibliographic record
Abstract
Inflammatory bowel disease (IBD) is a highly prevalent condition characterized by chronic inflammation present along the gastrointestinal (GI) tract. Mitigation of symptoms is critical to the quality of life of patients. Targeting Mucosal Addressin-Cell Adhesion Molecule 1 (MAdCAM-1), a cell surface antigen predominantly expressed on endothelial cells of venules located in the lamina propria of the small intestine and colon, represents an attractive marker to locally deliver therapeutics that dampen inflammation associated with IBD. As such, mAbs derived from eight hybridoma clones were characterized, shown to bind to human MAdCAM-1 with dissociation constants in the low to sub-nanomolar range and were able to detect human MAdCAM-1 transiently expressed on the surface of cells. Interestingly, only 4 of these antibodies detected MAdCAM-1 on the venules of human small intestinal tissue by immunohistochemistry. Importantly, these 4 antibody clones, 1B10, 11C3, 7A2, and 2F3 behave as strong antagonists, able to block MAdCAM-1 costimulation of primary human CD4 + T cells. These antibodies or related anti hMaDCAM-1 scFv bispecifics may serve as targeted therapeutics to the GI tract for treating IBD.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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".