# CAR-T against stroma: fibroblasts and myeloid cells

Source: https://onco.cc/technologies/stroma-directed-car/  
OnCo record `stroma-directed-car` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Instead of attacking the cancer cell, engineering T cells to strip away the scaffolding and the suppressive immune cells that protect it.

## Summary

FAP-directed CAR-T depletes cancer-associated fibroblasts and, in mouse models, opens desmoplastic tumours to chemotherapy and immunity; a small Swiss study delivered FAP CAR-T into the pleural cavity in mesothelioma. Myeloid-directed approaches target CSF1R, TREM2, or CD163 populations. The recurring problem is that FAP and myeloid markers are not tumour-specific: FAP is expressed in bone-marrow stroma and healing tissue, and murine FAP CAR-T caused cachexia and marrow toxicity in early studies.

## Fields

- Kind: Technology
- Status: preclinical
- Last checked: 2026-09-08
- Tags: frontier; radical
- Principle: A CAR recognises a stromal antigen rather than a tumour antigen; killing the supporting cells collapses the niche the tumour depends on.
- Strengths: Stroma is genetically stable, so it cannot mutate away; One construct could serve many cancers; Combines with drugs that stroma currently blocks
- Limitations: On-target off-tumour toxicity: marrow, wound healing, cachexia; No registrational programme; Depleting stroma accelerated disease in some pancreatic models

## Sources

- ClinicalTrials.gov: FAP CAR-T: https://clinicaltrials.gov/search?term=FAP%20CAR-T

## Connected records

- cancers: [Mesothelioma](https://onco.cc/cancers/mesothelioma/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- fronts: [Cell Therapy](https://onco.cc/fronts/cell-therapy/), [Immunotherapy](https://onco.cc/fronts/immunotherapy/)
- technologies: [Armoured, logic-gated & next-gen CARs](https://onco.cc/technologies/armored-car/), [CAR-T cell therapy](https://onco.cc/technologies/car-t/), [FAPI PET](https://onco.cc/technologies/fapi-pet/)
- targets: [FAP](https://onco.cc/targets/fap/)
- roadmaps: [Radical oncology: what could change the war by 2035](https://onco.cc/roadmaps/frontier-2035/)
- pathways: [Fibroblast activation, desmoplasia & matrix stiffness](https://onco.cc/pathways/caf-activation-desmoplasia/)

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