Engineering a single-chain immunoglobulin scaffold loaded with a latent-releasable cytotoxic pore-forming peptide
Bibliographic record
Abstract
Pore-forming peptides (PFPs) hold strong anti-tumor potential but require delivery systems to ensure stability and prevent off-target effects. In this study, we develop a strategy to transport a PFP in a biologically latent, precursor-like state. Specifically, based on the therapeutic antibody atezolizumab, which targets the tumor-associated programmed death-ligand 1, we engineered a single-chain IgG (scIgG) construct with flexible linkers embedding the melittin sequence. To further enable tumor-specific activation, melittin was flanked by regions cleavable by matriptase/ST14 (MT), a protease overexpressed in carcinomas. Initial constructs failed due to cytotoxicity during expression, prompting the redesign of melittin into a variant named Pmod2-2. This peptide retained potent pore-forming ability and was compatible with IgG fusion. The resulting scIgG-Pmod2-2 hybrid preserved Fab and Fc functionalities of the atezolizumab IgG, displayed favorable pharmacokinetics and released the active peptide in response to MT. These results highlight the potential of integrating cytolytic PFPs into antibody-based therapeutics.
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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) | 0.000 | 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 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".