TCR transgenes and transgene cassettes for TCR gene therapy: status in 2008.
The genetic introduction of T cell receptor genes into T cells has been developed over the past decade as a strategy to induce defined antigen-specific T cell immunity. With the potential value of TCR gene therapy well-established in murine models and the feasibility of infusion of TCR-modified autologous T cells shown in a first phase I trial, the next key step will be to transform TCR gene transfer from an experimental technique into a robust clinical strategy. In this review, we discuss the different properties of the TCR transgene and transgene cassette that can strongly affect both the efficacy and the safety of TCR gene transfer.
Uckert
Wolfgang
W
Department of Molecular Cell Biology and Gene Therapy, Max-Delbrück-Center of Molecular Medicine, Robert-Rössle-Strasse 10, Berlin, Germany. wuckert@mdc-berlin.de
Schumacher
Ton N M
TN
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D017321:Clinical Trials, Phase I as Topic / Q000706:statistics & numerical data; D003062:Codon / Q000235:genetics; D019281:Dimerization; D005240:Feasibility Studies; D005813:Genes, Synthetic; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D005822:Genetic Vectors / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods*; D058965:MART-1 Antigen; D008545:Melanoma / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000276:immunology; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation; D019076:Transgenes
D000951:Antigens, Neoplasm; D003062:Codon; D058965:MART-1 Antigen; C548667:MLANA protein, human; C548668:Mlana protein, mouse; D009363:Neoplasm Proteins; D011948:Receptors, Antigen, T-Cell