Abstract: The disclosure provides methods and materials useful for obtaining novel TCR gene sequences that are useful in tumor-specific T cell receptor (TCR) gene transfer. Embodiments of the invention also include methods of crosslinking and permeabilizing mammalian cells that can, for example, be used in methods for obtaining novel TCR gene sequences. The disclosure further provides methods and materials useful for obtaining novel TCR gene sequences. Tumor-specific T cell receptor gene transfer enables specific and potent immune targeting of tumor and viral antigens, and for this reason is technology of significant interest to medical personnel.

Abstract: Tumor-specific T cell receptor (TCR) gene transfer enables specific and potent immune targeting of tumor antigens. The canonical cancer-testis antigen, NY-ESO-1, is not expressed in normal tissues but is aberrantly expressed across a broad array of cancer types. It has also been targeted with A2-restricted TCR gene therapy without adverse events or notable side effects. To enable the targeting of NY-ESO-1 in a broader array of HLA haplotypes, we isolated TCRs specific for NY-ESO-1 epitopes presented by four MHC molecules: HLA-A2, -B07, -B18, and -C03. Using these TCRs, we have developed an approach to extend TCR gene therapies targeting NY-ESO-1 to patient populations beyond those expressing HLA-A2.