Rewiring endogenous genes in CAR T cells for tumour-restricted payload delivery



Summary

Rewiring CAR T cells to deliver therapeutic payloads directly within the tumor microenvironment offers a promising strategy to enhance efficacy and reduce systemic toxicity. This approach involves using endogenous genes, already active in CAR T cells upon target engagement, as drivers for payload expression. By replacing the endogenous protein with a therapeutic one under the control of the same regulatory elements, payload delivery becomes tumor-restricted and triggered only when the CAR T cell recognizes and interacts with the cancer cell. This ensures potent anti-tumor activity at the site of the tumor while minimizing off-target effects and improving the overall safety profile of CAR T cell therapy.

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