CHIMERIC RECEPTOR PROTEINS AND USES THEREOF

Smart overview of the Invention

The disclosure introduces fusion proteins with enhanced signaling properties, particularly beneficial in targeting antigens expressed at varying levels on cells such as solid tumor cells. These proteins are composed of an extracellular antigen-binding domain, a transmembrane domain, and an intracellular component with domains or motifs from CD3ε, γ, or δ proteins. The invention also encompasses recombinant host cells expressing these proteins and related compositions and methods.

Government Support and Sequence Listing

This development received support from the National Institutes of Health under grants CA136551 and CA114536. The associated sequence listing is submitted electronically, detailing the specific sequences involved in these fusion proteins.

Background and Need

Adoptive transfer of genetically modified T cells is a promising therapy for malignancies. Chimeric antigen receptors (CARs) have been used to target tumor-associated antigens effectively. Despite progress, there is a need for improved CAR functionality, especially for targeting antigens in solid tumors. The disclosed fusion proteins aim to address these challenges by enhancing signaling responses.

Detailed Description

The fusion proteins are designed to improve signaling when binding to antigens on target cells such as cancer cells. They include an extracellular binding domain, a transmembrane domain, and an intracellular component with various motifs like ITAMs from CD3ε, γ, or δ. These components enhance signal initiation and propagation within host cells like T cells upon antigen binding.

Applications and Benefits

The fusion proteins can be utilized in cellular immunotherapies involving host cells that express them to target disease-associated antigens effectively. Host cells expressing these proteins show improved signaling and activity against low or intermediate antigen-expressing cells, potentially leading to better therapeutic outcomes in cancer treatment by reducing tumor growth and increasing patient survival.