Generation, Expression, and Monitoring of Recombinant Immune Receptors for Use in Cellular Immunotherapy

Cellular immunotherapy has attracted increasing interest in genetic modification of immunologically competent cells in order to activate the effector cell after binding to predefined antigen. The chimeric immune-receptor strategy utilizes recombinant receptor molecules that are grafted on the surface of effector cells and comprise an extracellular antigen-binding domain and an intracellular signaling domain. The antigen-binding domain is a scFv (single-chain fragment of variable regions) derived from an antibody and is fused to a transmembrane moiety and an intracellular signaling domain that mediates cellular activation upon receptor crosslinking by binding of the scFv domain to antigen. This design of a chimeric receptor molecule combines the specific binding to predefined ligands with the initiation of intracellular signaling pathways for cellular activation (1 ).