OnCo
ideasIdea

Grow immune command posts inside tumours

Tumours that contain small immune structures resembling lymph nodes respond far better to immunotherapy. Inducing those structures on purpose could make cold tumours responsive.

Tertiary lymphoid structures and B-cell aggregates are among the strongest predictors of checkpoint response in sarcoma, melanoma and renal cancer. Their formation depends on LIGHT, lymphotoxin, CXCL13 and stromal organiser cells, and vascular-targeted LIGHT fusions induced them in mouse tumours. No clinical programme currently has tertiary lymphoid structure induction as its declared primary mechanism.

Hypothesis
An induction regimen based on LIGHT or CXCL13 delivery generates measurable tertiary lymphoid structures in serial biopsies of cold tumours, and their appearance is accompanied by intratumoural clonal T-cell expansion.
Rationale
The association between these structures and response is unusually strong and reproducible across tumour types and datasets, and murine induction is achievable. Sarcoma trials already stratify by a B-cell-rich immune class, providing a ready-made target population.
What would test it
Phase 1 with mandatory serial biopsies in immune-class-defined sarcoma or renal cancer, primary endpoint the histological appearance of new lymphoid structures, secondary endpoint T-cell clonal expansion.
Maturity
preclinical evidence
Who has to act
research
Cost to try
Medium ($1M to $50M)
Years to first evidence
8
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