Human natural killer cell line modified with a chimeric immunoglobulin T-cell receptor gene leads to tumor growth inhibition in vivo.
The gene transfer of tumor-specific chimeric immunoglobulin T-cell receptors (cIgTCRs) combining antibody-like specificity with the effector cell function could be an attractive tool in immunotherapy. In this study, we directed the human natural killer (NK) cell line YT to tumor cells by gene transfer of a cIgTCR with specificity against the human carcinoembryonic antigen (CEA). The cIgTCR was constructed of a CEA-specific humanized single-chain Fv antibody fragment fused to the IgG1 Fc domain and the CD3 zeta chain. YT cells were transfected with the cIgTCR gene by electroporation and cIgTCR-expressing cells were enriched by immunoaffinity purification. cIgTCR-expressing YT cells specifically lysed CEA(+) colon carcinoma cell lines, which were resistant to the parental YT cell line. The lysis was not inhibited in the presence of soluble CEA. Receptor gene-modified YT cells retained their CEA-specific cytolytic activity after gamma-irradiation in vitro and inhibited the tumor growth in vivo after adoptive transfer into NOD/SCID mice. This gene-modified NK cell line available in unlimited source might be useful in clinical immunotherapy of CEA(+) cancer.
Schirrmann
Thomas
T
Department of Internal Medicine, Medical Oncology and Hematology, AG Molecular Gene and Immunotherapy, Humboldt-University Berlin, Charité Campus Mitte, 10115 Berlin, Germany.
Pecher
Gabriele
G
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D017931:DNA Primers / Q000737:chemistry; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D005434:Flow Cytometry; D005720:Gamma Rays; D019672:Genes, T-Cell Receptor / Q000276:immunology*; D005822:Genetic Vectors; D006801:Humans; D007128:Immunoglobulin Fragments / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000528:radiation effects; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009369:Neoplasms / Q000628:therapy*; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D019139:Tumor Escape
D000951:Antigens, Neoplasm; D017252:CD3 Complex; D002272:Carcinoembryonic Antigen; D017931:DNA Primers; D007128:Immunoglobulin Fragments; D011993:Recombinant Fusion Proteins