MODIFIED IMMUNE CELLS HAVIG ENHANCED FUNCTION AND METHODS FOR SCREENING THE SAME

Smart overview of the Invention

The patent application details the development of gene-edited immune cells, such as T cells, that have been modified to express an exogenous T cell receptor (TCR) or chimeric antigen receptor (CAR) targeting specific antigens. These modifications include insertions or deletions in endogenous gene loci that regulate T cell function, enhancing their immune response capabilities. The application also outlines compositions and therapeutic methods using these enhanced immune cells.

Background

The field of adoptive cell therapy has progressed significantly, particularly with CAR- and TCR-engineered T cells, providing new strategies for treating cancer, chronic infections, and autoimmune diseases. A major challenge in this therapy is overcoming T cell exhaustion and immunosuppressive environments that hinder effective treatment. This patent addresses the need to identify genes that regulate TCR- or CAR-engineered T cell functions to improve therapeutic outcomes.

Innovation

The invention introduces a genome-wide screening method to identify genes that enhance T cell functions such as efficacy, memory, and persistence. By downregulating specific genes through insertions or deletions, the modified T cells exhibit improved immune functions. The patent highlights the use of CRISPR/Cas9 technology for precise genetic modifications to achieve these enhancements.

Specific Modifications

Key genetic modifications involve transcriptional modulators like SIX2 and KLF4, which are downregulated to enhance T cell function. Additionally, epigenetic regulators such as components of histone methyltransferase complexes are targeted. The application provides examples of gene loci modifications that lead to enhanced immune responses by altering expression patterns of specific proteins.

Applications

The modified immune cells are designed for various therapeutic applications, including cancer treatment. They incorporate exogenous TCRs or CARs with specific structural domains to increase affinity and functional performance against target antigens. The modifications allow for improved persistence and efficacy in clinical settings, potentially leading to better patient outcomes in diseases traditionally resistant to conventional therapies.