T cell Receptor Discovery and Engineering Platform
Immatics’ XCEPTOR™ platform enables fast and efficient discovery, engineering and validation of a large number of high-affinity and highly specific natural TCRs that can be used for Adoptive Cell Therapies i.e. ACTengine®, ACTallo® and TCR Bispecifics.
T cell Receptor Discovery
TCRs naturally recognize human HLA-bound peptides (“pHLA targets”) derived from foreign and endogenous proteins, regardless of their extracellular or intracellular localization. Immatics has established XCEPTOR™, a next-generation technology platform designed to discover, engineer and validate TCRs. The process comprises the discovery and selection of highly specific parental, membrane-bound TCRs with optional engineering to serve ACT modalities, and further engineering via affinity-maturation for TCR Bispecifics (TCER™).
Key features of XCEPTOR™ include:
- Many unique TCRs are identified for each target in a high throughput approach and for several targets in parallel.
- Multiple TCR sources are used for each target, such as blood cells from many different HLA-matched and HLA-mismatched donors or patients.
- TCRs are re-expressed in human donor cells, extensively screened in vitro (e.g. testing of killing of tumor cell lines vs normal cells to establish a therapeutic window) and qualified as candidates for Adoptive Cell Therapies or TCR Bispecifics.
- Information exchange with the XPRESIDENT® platform throughout TCR identification and candidate screening ensures selection of specific and potent TCRs, e.g. by providing information on TCR-motif and target similar peptide expression on healthy tissue, or calibrated tumor cell lines with physiological target levels as screening tool.
- Qualified TCRs are subject to further engineering, including affinity maturation, engineering towards CD8 independency or chain pairing enhancement, if needed.
To further advance its technologies, Immatics has developed TCR Scout™, a new member of the Immatics’ platform technologies, that allows high-throughput kinetic screenings of pHLA ligands and potential clinical lead candidates (TCRs, antibodies).