Data from Identification and Validation of T-cell Receptors Targeting <i>RAS</i> Hotspot Mutations in Human Cancers for Use in Cell-based Immunotherapy

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<div>AbstractPurpose:<p>Immunotherapies mediate the regression of human tumors through recognition of tumor antigens by immune cells that trigger an immune response. Mutations in the <i>RAS</i> oncogenes occur in about 30% of all patients with cancer. These mutations play an important role in both tumor establishment and survival and are commonly found in hotspots. Discovering T-cell receptors (TCR) that recognize shared mutated RAS antigens presented on MHC class I and class II molecules are thus promising reagents for “off-the-shelf” adoptive cell therapies (ACT) following insertion of the TCRs into lymphocytes.</p>Experimental Design:<p>In this ongoing work, we screened for RAS antigen recognition in tumor-infiltrating lymphocytes (TIL) or by <i>in vitro</i> stimulation of peripheral blood lymphocytes (PBL). TCRs recognizing mutated RAS were identified from the reactive T cells. The TCRs were then reconstructed and virally transduced into PBLs and tested.</p>Results:<p>Here, we detect and report multiple novel TCR sequences that recognize nonsynonymous mutant RAS hotspot mutations with high avidity and specificity and identify the specific class-I and -II MHC restriction elements involved in the recognition of mutant RAS.</p>Conclusions:<p>The TCR library directed against RAS hotspot mutations described here recognize RAS mutations found in about 45% of the Caucasian population and about 60% of the Asian population and represent promising reagents for “off-the-shelf” ACTs.</p></div>