Gene transfer of MHC-restricted receptors.
Adoptive therapy with allogeneic or tumor-specific T-cells has shown substantial clinical effects for several human tumors, but the widespread application of this strategy remains a daunting task. The antigen specificity of T-lymphocytes is solely determined by the T-cell receptor (TCR) alpha and beta chains. Consequently, genetic transfer of TCR chains may form an alternative and potentially appealing strategy to impose a desirable tumor-antigen specificity onto cytotoxic or helper T-cell populations. In this strategy, autologous or donor-derived T-cell populations are equipped with a TCR of defined reactivity in short-term ex vivo cultures, and re-infusion of the redirected cells is used to supply T-cell reactivity against defined tumor-specific antigens. We have previously described the genetic introduction of T-cell receptor genes into peripheral T-cells in mouse model systems. Here we discuss the requirements for the successful genetic modification of murine T-lymphocytes and the subsequent use of such genetically modified cells in in vivo models.
Kessels
Helmut W H G
HW
Department of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Wolkers
Monika C
MC
Schumacher
Ton N M
TN
D019264:Adoptive Transfer; D000818:Animals; D002478:Cells, Cultured; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006649:Histocompatibility Antigens / Q000276:immunology*; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification; D012192:Retroviridae Infections / Q000235:genetics / Q000821:virology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000821:virology
D006649:Histocompatibility Antigens; D011948:Receptors, Antigen, T-Cell