US20250297259
2025-09-25
Chemistry; metallurgy
C12N15/1137
The application details an engineered immune cell with the CIITA gene knocked out, utilizing a specifically designed sgRNA. This approach aims to create universal CAR-T cells with high knockout efficiency, offering potential in cancer immunotherapy and treatment of various diseases. The engineered cells can be used for allotransplantation, reducing preparation time and costs associated with current CAR-T therapies.
Positioned within the biomedicine field, the invention focuses on modifying immune cells, particularly T cells, to enhance their therapeutic potential. The CIITA gene is targeted due to its role in controlling MHC class II molecule expression, which is crucial for immune response regulation and preventing graft-versus-host disease (GvHD) and host-versus-graft disease (HvGD).
CAR-T cell immunotherapy has shown significant promise in treating hematological tumors, with FDA-approved therapies for specific cancers. However, challenges such as high costs and lengthy preparation times hinder widespread adoption. Universal CAR-T products derived from healthy donors could address these issues by offering faster and potentially more effective treatments.
The invention provides an sgRNA with specific spacer sequences to target the CIITA gene effectively. It includes methods for introducing Cas nucleases like Cas9 into immune cells to achieve gene knockout. This process can be applied to various immune cells, including T cells and NK cells, enhancing their ability to target cancer antigens through engineered receptors.
The engineered immune cells can be used for disease prevention, treatment, and diagnosis of cancer, infections, or autoimmune diseases. By designing chimeric antigen receptors that bind to specific targets like CD19 or CD22, the technology promises improved therapeutic outcomes. Moreover, it offers a scalable solution for creating versatile CAR-T therapies suitable for diverse medical conditions.