Shieldbreaks¶
A "shieldbreak" is a single project query — one research question about a mechanism of resistance to a cancer immunotherapy (checkpoint blockade, adoptive cell therapy, vaccine, cytokine, bispecific, oncolytic virus, or other immuno-oncology modality), with its own search parameters, extraction schema, trial table, and manuscript critique. Each lives in its own subdirectory so it can evolve independently of the others.
Active shieldbreaks¶
| Shieldbreak | Rows | Last updated | Critique |
|---|---|---|---|
| Treg Depletion and/or Inhibition | 51 | 2026-04-23 | critique |
| Tumor-associated Macrophage Depletion, Inhibition, or Repolarization | 37 | 2026-04-24 | critique |
Adding a shieldbreak¶
Invoke the trialist_screener Claude Code subagent and answer "new shieldbreak" when prompted. The agent will:
- Ask for a project name and propose a slug (kebab-case)
- Elicit the search parameters → write to
prompts/shieldbreaks/<slug>/search.md - Elicit the extraction schema → write to
prompts/shieldbreaks/<slug>/extract.mdanddata/shieldbreaks/<slug>/schema.json - Run the search, screen, extract → append to
data/shieldbreaks/<slug>/trials.jsonl - Generate
docs/shieldbreaks/<slug>/index.mdwith the trial table - Add a row to this index page linking to the new project
Once a shieldbreak has trial rows, the companion trialist_skeptic subagent reads the ingested manuscripts in full, verifies the extracted fields against the source, and publishes docs/shieldbreaks/<slug>/critique.md — a per-paper and cross-paper methodological appraisal. The skeptic also assesses, for every paper, counter-productive mechanisms by which the intervention's MoA may undermine the shieldbreak's broader target effect (e.g., anti-CCR4 depleting CCR4+ CD8 effector-memory cells alongside Tregs) even when the proximal endpoint is met.
With the screener and skeptic runs complete, the trialist_prescriber subagent then synthesizes a top-level narrative: it reads trials.jsonl and critiques.jsonl, groups rows into interventions or intervention classes under PI-confirmed granularity, and for each selected intervention (3–7 total) writes a short section covering evidence base, likelihood of the desired effect, toxicity profile, counter-productive mechanisms, practical considerations, and a ranked-position rationale. The output is published as docs/shieldbreaks/<slug>/scope_summary.md and inlined at the top of the shieldbreak page under the ## Scope summary heading; a Ranked prioritization table at the end weighs Likelihood × Toxicity × Counter-productive MoA into an Overall column. Rankings reflect the shieldbreak's Target effect as written; re-scoping it toward a downstream goal shifts the weights.