Development of a novel antibody–tetrazine conjugate for bioorthogonal pretargeting
Why this work is in the frame
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Bibliographic record
Abstract
Recently, bioorthogonal chemistry based on the Inverse Electron-Demand Diels-Alder (IEDDA) cycloaddition between 1,2,4,5-tetrazines and trans-cyclooctene (TCO) analogues added an interesting dimension to molecular imaging. Until now, antibodies (Abs) were tagged with TCO and after pretargeting they were reacted with tetrazines substituted with reporters. However, TCO tags have the tendency to degrade under physiological conditions, and due to their hydrophobic nature are buried within the protein. This results in loss of reactivity and a low Ab functional loading. To circumvent these problems, we report for the first time an approach in which tetrazines are used as tags for antibody (Ab) modification, and TCO as the imaging agent. We developed a new Ab-tetrazine conjugate, which displays a high functional loading, good stability and reactivity. We utilized this immunoconjugate for live-cell imaging together with novel TCO probes, resulting in selective and rapid labeling of SKOV-3 cells. Our approach may be useful for in vivo pretargeted imaging.
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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) | 0.002 | 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 it