Designing TCR for cancer immunotherapy.
Reprogramming T-cell populations by T-cell receptor (TCR) gene transfer is a new therapeutic tool for adoptive tumor immunotherapy. Gene transfer of human leukocyte antigen (HLA)-transgenic mice-derived TCR into human T-cells allows the circumvention of tolerance to tumor-associated (self) antigens (TAA). This chapter reports on the identification of the alpha and beta chains of the heterodimeric TCR derived from a mouse T-cell clone. The related DNA fragments are inserted into a retroviral vector for heterologous expression of the TAA-specific TCR in human T-cells. Polymerase chain reaction (PCR)-based cloning protocols are provided for the tailor-made customization of murine TCR. We describe the humanization and chimerization of such TCR as well as their expression in human T-cells.
Voss
Ralf-Holger
RH
Department of Hematology and Oncology, Johannes Gutenberg-University, Mainz, Germany.
Kuball
Jürgen
J
Theobald
Matthias
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013379:Substrate Specificity; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D011948:Receptors, Antigen, T-Cell