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Abstract
In situ CAR-macrophage therapy demonstrates robust CAR expression directly within the tumor microenvironment.
- Codelivery of mRNA and an immunostimulant using lipid nanoparticles facilitates direct targeting of tumor-associated macrophages.
- This method avoids the limitations of ex vivo manipulation, which can hinder gene transfer and macrophage phenotype maintenance.
- The addition of a stimulator of interferon genes (STING) agonist enhances local immune activation.
- In a mouse melanoma model, the approach reinforces CAR-macrophage functionality and improves antitumor effects.
- The findings indicate potential for an LNP-enabled strategy to address challenges faced by traditional CAR-T cell therapies.
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