RT Journal Article
SR Electronic
T1 Antigen-specific <em>In Vitro</em> Expansion of Functional Redirected NY-ESO-1-specific Human CD8<sup>+</sup> T-Cells in a Cell-free System
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 4189
OP 4201
VO 33
IS 10
A1 GOPINADH JAKKA
A1 PETRA C. SCHUBERTH
A1 MARKUS THIEL
A1 GERHARD HELD
A1 FRANK STENNER
A1 MARIES VAN DEN BROEK
A1 CHRISTOPH RENNER
A1 AXEL MISCHO
A1 ULF PETRAUSCH
YR 2013
UL http://ar.iiarjournals.org/content/33/10/4189.abstract
AB Background: Tumors can be targeted by the adoptive transfer of chimeric antigen receptor (CAR) redirected T-cells. Antigen-specific expansion protocols are needed to generate large quantities of redirected T-cells. We aimed to establish a protocol to expand functional active NY-ESO-1-specific redirected human CD8+ T-cells. Materials and Methods: The anti-idiotypic Fab antibody A4 with specificity for HLA-A*0201/NY-ESO-1157-165 was tested by competition assays using a HLA-A*0201/NY-ESO-1157-165 tetramer. HLA-A*0201/NY-ESO-1157-165 redirected T-cells were generated, expanded and tested for CAR expression, cytokine release, in vitro cytolysis and protection against xenografted HLA-A*0201/NY-ESO-1157-165–positive multiple myeloma cells. Results: A4 demonstrated antigen-specific binding to HLA-A*0201/NY-ESO-1157-165 redirected T-cells. Expansion with A4 resulted in 98% of HLA-A*0201/NY-ESO-1157-165 redirected T-cells. A4 induced strong proliferation, resulting in a 300-fold increase of redirected T-cells. After expansion protocols, redirected T-cells secreted Interleukin-2, (IL-2), interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα) and lysed target cells in vitro and were protective in vivo. Conclusion: A4 expanded HLA-A*0201/NY-ESO-1157-165 redirected T-cells with preservation of antigen-specific function.