title: High-throughput identification of antigen-specific TCRs by TCR gene capture.
abstract: The transfer of T cell receptor (TCR) genes into patient T cells is a promising approach for the treatment of both viral infections and cancer. Although efficient methods exist to identify antibodies for the treatment of these diseases, comparable strategies to identify TCRs have been lacking. We have developed a high-throughput DNA-based strategy to identify TCR sequences by the capture and sequencing of genomic DNA fragments encoding the TCR genes. We establish the value of this approach by assembling a large library of cancer germline tumor antigen-reactive TCRs. Furthermore, by exploiting the quantitative nature of TCR gene capture, we show the feasibility of identifying antigen-specific TCRs in oligoclonal T cell populations from either human material or TCR-humanized mice. Finally, we demonstrate the ability to identify tumor-reactive TCRs within intratumoral T cell subsets without knowledge of antigen specificities, which may be the first step toward the development of autologous TCR gene therapy to target patient-specific neoantigens in human cancer.
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Carsten
authors.initials: C
authors.lastname: Linnemann
authors.forename: Bianca
authors.initials: B
authors.lastname: Heemskerk
authors.forename: Pia
authors.initials: P
authors.lastname: Kvistborg
authors.forename: Roelof J C
authors.initials: RJ
authors.lastname: Kluin
authors.forename: Dmitriy A
authors.initials: DA
authors.lastname: Bolotin
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Chen
authors.forename: Kaspar
authors.initials: K
authors.lastname: Bresser
authors.forename: Marja
authors.initials: M
authors.lastname: Nieuwland
authors.forename: Remko
authors.initials: R
authors.lastname: Schotte
authors.forename: Samira
authors.initials: S
authors.lastname: Michels
authors.forename: Raquel
authors.initials: R
authors.lastname: Gomez-Eerland
authors.forename: Lorenz
authors.initials: L
authors.lastname: Jahn
authors.forename: Pleun
authors.initials: P
authors.lastname: Hombrink
authors.forename: Nicolas
authors.initials: N
authors.lastname: Legrand
authors.forename: Chengyi Jenny
authors.initials: CJ
authors.lastname: Shu
authors.forename: Ilgar Z
authors.initials: IZ
authors.lastname: Mamedov
authors.forename: Arno
authors.initials: A
authors.lastname: Velds
authors.forename: Christian U
authors.initials: CU
authors.lastname: Blank
authors.forename: John B A G
authors.initials: JB
authors.lastname: Haanen
authors.forename: Maria A
authors.initials: MA
authors.lastname: Turchaninova
authors.forename: Ron M
authors.initials: RM
authors.lastname: Kerkhoven
authors.forename: Hergen
authors.initials: H
authors.lastname: Spits
authors.forename: Sine Reker
authors.initials: SR
authors.lastname: Hadrup
authors.forename: Mirjam H M
authors.initials: MH
authors.lastname: Heemskerk
authors.forename: Thomas
authors.initials: T
authors.lastname: Blankenstein
authors.forename: Dmitriy M
authors.identifier: 000000030430790X
authors.initials: DM
authors.lastname: Chudakov
authors.forename: Gavin M
authors.initials: GM
authors.lastname: Bendle
authors.forename: Ton N M
authors.initials: TN
authors.lastname: Schumacher
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D015723:Gene Library; D019672:Genes, T-Cell Receptor; D015316:Genetic Therapy; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D011948:Receptors, Antigen, T-Cell