Method of Neoantigen-Reactive T Cell Receptor (TCR) Isolation from Peripheral Blood of Cancer Patients

Adoptive cell transfer (ACT) uses tumor infiltrating lymphocytes (TILs) that recognize antigens expressed by cancer cells (neoantigens). Neoantigen specific TIL administration in patients has resulted in long-term regression of certain metastatic cancers. However, current procedures for TIL therapy are highly invasive, labor-intensive, and time consuming. The success of these procedures is limited and differs between patients and histologies. Isolation of neoantigen reactive TCRs have historically been challenging due to very low precursor frequencies of these T-cells as well as lack of technical advances that can determine phenotypic markers of these cells from the blood.  Researchers at the National Cancer Institute (NCI) have developed a novel method for isolation and construction of neoantigen-reactive T-cell receptors (TCRs) from peripheral blood lymphocytes (PBL) of cancer patients.   This method allows direct isolation of T cells from the blood, based on a distinct T cell gene signature; thus, it does not require tumor cells to be gown or propagated in vitro. In this method, peptide-HLA tetramers (pHLA) are used to isolate neoantigen reactive T cells based on patient specific information on major histocompatibility complex and tumor specific mutations. By taking advantage of the unique genetic signatures of neoantigen specific T cells, this method not only generates accurate scoring of single T cells from tumors, but also facilitates identification and reconstruction...
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