Development of a cyst-targeted therapy for polycystic kidney disease using an antagonistic dimeric IgA monoclonal antibody against cMET
Bibliographic record
Abstract
Polycystic kidney disease (PKD) is characterized by the development of fluid-filled kidney cysts and relentless progression to renal failure. Current treatments have adverse effects and limited efficacy, enhancing the need for improved therapeutics. Here, we provide a proof of concept for the use of dimeric immunoglobulin A (IgA) (dIgA) monoclonal antibodies (mAbs) to target epithelial-enclosed cysts, by exploiting their ability to transcytose via the polymeric immunoglobulin receptor highly expressed on renal cyst-lining cells. We engineered an antagonistic dIgA mAb against the cell mesenchymal-epithelial transition (cMET) receptor, a driver of cyst progression, and demonstrated its specific binding and inhibition of cMET in vitro. In vivo studies in PKD rodent models showed efficient targeting of the mAb to renal cyst lumens and its ability to slow disease progression without apparent adverse effects. This study presents an intriguing avenue for developing antibody-based therapies for PKD and similar diseases by repurposing existing immunoglobulin G (IgG) mAbs into dIgA mAbs for superior targeting to epithelial-enclosed compartments.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".