Functional human antigen-specific T cells produced in vitro using retroviral T cell receptor transfer into hematopoietic progenitors.
In vitro production of human T cells with known Ag specificity is of major clinical interest for immunotherapy against tumors and infections. We have performed TCRalphabeta gene transfer into human hemopoietic progenitors from postnatal thymus or umbilical cord blood, and subsequently cultured these precursors on OP9 stromal cells expressing the Notch human ligand Delta-like1. We report here that fully mature, functional T cells with controlled Ag specificity are obtained from such cultures. Using vectors encoding TCRalphabeta-chains directed against melanoma (MART-1), viral (CMV), and minor histocompatibility (HA-2) Ags, we show that the obtained Ag-specific T cells exert cytolytic activity against their cognate Ag and expand in vitro upon specific TCR stimulation. Therapeutic applications may arise from these results because they provide a way to produce large numbers of autologous mature Ag-specific T cells in vitro from undifferentiated hemopoietic progenitors.
van Lent
Anja U
AU
Department of Cell Biology and Histology, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
Nagasawa
Maho
M
van Loenen
Marleen M
MM
Schotte
Remko
R
Schumacher
Ton N M
TN
Heemskerk
Mirjam H M
MH
Spits
Hergen
H
Legrand
Nicolas
N
D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology*; D002460:Cell Line; D002675:Child, Preschool; D018920:Coculture Techniques; D018984:Epitopes, T-Lymphocyte / Q000502:physiology*; D018014:Gene Transfer Techniques; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D012190:Retroviridae / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D014161:Transduction, Genetic
D018984:Epitopes, T-Lymphocyte; D016693:Receptors, Antigen, T-Cell, alpha-beta