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Antigen-specific in vitro expansion of functional redirected NY-ESO-1-specific human CD8+ T-cells in a cell-free system


Jakka, Gopinadh; Schuberth, Petra C; Thiel, Markus; Held, Gerhard; Stenner, Frank; van den Broek, Maries; Renner, Christoph; Mischo, Axel; Petrausch, Ulf (2013). Antigen-specific in vitro expansion of functional redirected NY-ESO-1-specific human CD8+ T-cells in a cell-free system. Anticancer Research, 33(10):4189-4201.

Abstract

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.

Abstract

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Oncology
04 Faculty of Medicine > Institute of Experimental Immunology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2013
Deposited On:15 Oct 2013 09:08
Last Modified:05 Apr 2016 17:03
Publisher:International Institute of Anticancer Research
ISSN:0250-7005
Free access at:Publisher DOI. An embargo period may apply.
Official URL:http://ar.iiarjournals.org/content/33/10/4189.abstract

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