Anti-TGFβ peptide P144 augments CAR-T cell efficacy through neutrophil recruitment and TME remodeling in malignant mesothelioma

Secreting the anti-TGFβ peptide P144 from mesothelin- or FAP-targeted CAR-T cells increases intratumoral neutrophils by ~three-fold and improves tumour control in AE17m mesothelioma.

• Why it matters: Malignant mesothelioma’s immunosuppressive, TGFβ-driven tumour microenvironment limits CAR-T activity in solid tumours, creating a need for strategies that locally counter TGFβ.
• What they did: Murine CAR-T cells targeting mesothelin (M11) or fibroblast activation protein (FAP) were engineered to secrete P144, then tested in co-culture and the syngeneic AE17m model; P144 was selected after stronger Smad3 suppression than P17 in vitro.
• The result: P144 secretion did not change transduction, expansion, or antigen-specific cytotoxicity, but increased antigen-driven IFNγ (especially at low effector-to-target ratios) and enhanced tumour growth control; neutrophil depletion reduced P144’s added benefit.

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