CHIMERIC RECEPTOR PROTEINS AND USES THEREOF

Smart overview of the Invention

Fusion proteins with enhanced signaling capabilities are introduced, specifically designed to improve responses to antigen binding. These proteins consist of three main components: an extracellular antigen-binding domain, a transmembrane domain, and an intracellular component that includes one or more domains from CD3ε, γ, or δ proteins. The improved signaling allows for effective targeting of antigens that may be expressed at low or intermediate levels on target cells, such as those found in solid tumors.

Government Support and Sequence Listing

The development of these chimeric receptor proteins received backing from the government through grants CA136551 and CA114536 from the National Institutes of Health, which establishes certain rights over the invention. Additionally, a Sequence Listing relevant to the application is provided in an electronic format, ensuring accessibility and incorporation into the specification.

Background and Need for Improved Therapies

Adoptive cell therapy using genetically modified T cells has shown promise in treating various cancers, particularly through the use of chimeric antigen receptors (CARs). While effective in targeting specific surface antigens on tumor cells, there remains a need for advancements that enhance CAR functionality, particularly in solid tumors where antigen expression may be less robust.

Detailed Description of Fusion Proteins

The disclosed fusion proteins are designed to initiate and amplify cellular signaling upon binding to antigens. They incorporate various functional domains from CD3 proteins, which are crucial for T cell activation. These proteins can be tailored to exclude certain domains while retaining essential signaling motifs, thus optimizing their effectiveness in immune responses against cancer cells.

Potential Applications and Benefits

These chimeric receptor proteins hold significant potential for cellular immunotherapies. Host cells expressing these proteins may exhibit enhanced signaling and activity when targeting antigens associated with tumors. This could lead to improved outcomes such as reduced tumor growth and increased survival rates compared to traditional therapies. The innovative design aims to provide a more effective treatment option for patients with malignancies.