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RB-340-1 is an experimental **autologous HER2-directed CAR-T cell therapy** that incorporates an inducible **CRISPR interference** circuit to suppress **programmed cell death protein 1** expression after antigen engagement. The product is engineered to express an anti-HER2 single-chain variable fragment CAR with **CD28** and **CD3 zeta** signaling domains, together with a TEV protease and an sgRNA targeting the **PDCD1** transcription start site; a second construct uses **LAT** fused to **dCas9-KRAB** through a TEV-cleavable sequence so that T-cell activation triggers localized transcriptional repression of PD-1. It was developed by **Ruby Biotech** as a single-product strategy intended for **HER2-positive cancers**, aiming to combine tumor targeting and checkpoint pathway suppression while avoiding the added cost and toxicity of administering separate checkpoint inhibitors.
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