Immunotherapy through TCR gene transfer.
The antigen specificity of T lymphocytes is dictated solely by the T cell receptor (TCR) alpha and beta chains. Consequently, genetic transfer of TCR chains may be an appealing strategy with which to impose a desirable virus- or tumor-antigen specificity onto cytotoxic or helper T cell populations. We describe here the genetic introduction of a virus-specific TCR into peripheral T cells in a mouse model system. These experiments showed that T cells redirected by TCR gene transfer expanded upon viral infection of mice and efficiently homed to effector sites. In this setting, TCR gene transfer was not associated with any significant autoimmune pathology. In addition, small numbers of TCR-transduced T cells promoted the rejection of antigen-expressing tumors in vivo. These data suggest that the redirection of T cells by TCR gene transfer is a viable strategy for the rapid induction of virus- or tumor-specific immunity.
Kessels
H W
HW
Division of Immunology, Department of Experimental Animal Pathology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
Wolkers
M C
MC
van den Boom
M D
MD
van der Valk
M A
MA
Schumacher
T N
TN
D000818:Animals; D001327:Autoimmune Diseases / Q000473:pathology; D002465:Cell Movement; D002478:Cells, Cultured; D019673:Genes, T-Cell Receptor alpha; D019674:Genes, T-Cell Receptor beta; D015316:Genetic Therapy; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000628:therapy*; D009976:Orthomyxoviridae Infections / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000637:transplantation*; D014161:Transduction, Genetic