Engineered high-affinity human t cell receptors
AssigneeThe Board of Trustees of the University of Illinois
InventorsSheena N. Smith, Daniel T. Harris, David M. Kranz
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Abstract
T cell receptors (TCRs) that have higher affinity for the Survivin antigen are provided. The high affinity TCRs were engineered through the generation of mutational libraries of TCRs in a single-chain format, followed by selection for improved stability and affinity on the surface of yeast (i.e. directed evolution). In embodiments, the engineered TCRs can be used in soluble form for targeted delivery in vivo, or as genes introduced into T cells in an adoptive T cell setting.
Claims17
A modified T cell receptor, or antigen-binding fragment thereof, comprising a Vα and a Vβ derived from a wild type T cell receptor, wherein the Vα or the Vβ, or both, comprise a mutation in one or more complementarity determining regions (CDRs) relative to the wild type T cell receptor, wherein the modified T cell receptor binds to a complex of the peptide Survivin and the HLA-A2 molecule with a nanomolar or higher affinity (KD value of less than 10−6M).
Dependencies are inferred from the claim text.