This technology is a CRISPR-based method for deleting endogenous T cell receptor (TCR) chains while preserving transgenic TCR functionality, enabling safer and more effective T cell therapies and the development of CAR-T cells.
Current methods for T cell therapy often involve genetic modifications that retain the endogenous T cell receptor (TCR). This can lead to mispairing with transgenic TCRs, reduced therapeutic efficacy, and potential autoimmune reactions. CRISPR-based approaches exist but struggle to effectively target both alpha and beta chains of the TCR and distinguish between endogenous and transgenic TCRs. Additionally, autologous CAR-T cell therapies are expensive and time-consuming to manufacture, limiting accessibility for patients. Addressing these limitations is critical to improve the safety, efficiency, and scalability of T cell therapies.
This technology is a CRISPR-based method to delete both the alpha and beta chains of the endogenous T cell receptor (TCR) without affecting the transgenic TCR. The endogenous TCR is deleted using CRISPR-based guide RNAs that target the intron-exon boundaries of the constant regions. The method preserves the integrity of the transgenic TCR, which lacks introns, ensuring its functionality is unaffected. By eliminating endogenous TCRs, this approach prevents mispairing and reduces the risk of generating receptors with unknown specificities. Additionally, the technology can be seamlessly integrated with transgenic TCR viral vectors to simultaneously delete endogenous TCRs and introduce transgenic TCR constructs.
This technology has been validated with human cancer cell lines.
Patent Pending (WO/2024/2588835)
IR CU20245, CU23372
Licensing Contact: Jerry Kokoshka