University of Illinois

Other

Fred Hutchinson Cancer Center

Sheena N Smith

David M Kranz

Daniel T Harris

Philip D Greenberg

Thomas M Schmitt

The use of model T cell receptors (TCRs) as scaffolds for in vitro engineering of novel specificities is provided. TCRs with de novo binding to a specific peptide-major histocompatibility complex (MHC) product can be isolated by: 1) mutagenizing a T cell receptor protein coding sequence to generate a variegated population of mutants (a library), 2) selection of the library of TCR mutants with the specific peptide-MHC, using a process of directed evolution and a 'display' methodology (e.g., yeast, phage, mammalian cell) and the peptide-MHC ligand. The process can be repeated to identify TCR variants with improved affinity for the selecting peptide-MHC ligand.

Engineering t cell receptors

T cell receptors (TCRs) that have specificity for the WT1 antigen are provided. The TCRs include higher affinity TCRs that 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 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.

Engineered high-affinity human t cell receptors

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.

Growing community of inventors

Urbana, IL, United States of America

Sheena N Smith