期刊
GENE THERAPY
卷 20, 期 4, 页码 386-395出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/gt.2012.48
关键词
NY-ESO-1; chimeric antigen receptor; multiple myeloma; memory T cells; CD8 T cells; re-directed T cells
类别
资金
- Dr Arnold U. und Susanne Huggenberger-Bischoff Stiftung zur Krebsforschung
- Cancer Research Institute
- Ludwig Institute of Cancer Research
- Krebsliga Zurich
The cancer-testis antigen NY-ESO-1 is a potential target antigen for immune therapy expressed in a subset of patients with multiple myeloma. We generated chimeric antigen receptors (CARs) recognizing the immunodominant NY-ESO-1 peptide 157-165 in the context of HLA-A*02:01 to re-direct autologous CD8(+) T cells towards NY-ESO-1(+) myeloma cells. These re-directed T cells specifically lysed NY-ESO-1(157-165)/HLA-A*02:01-positive cells and secreted IFN gamma. A total of 40% of CCR7(-) re-directed T cells had an effector memory phenotype and 5% a central memory phenotype. Based on CCR7 cell sorting, effector and memory CAR-positive T cells were separated and CCR7(+) memory cells demonstrated after antigen-specific re-stimulation downregulation of CCR7 as sign of differentiation towards effector cells accompanied by an increased secretion of memory signature cytokines such as IL-2. To evaluate NY-ESO-1 as potential target antigen, we screened 78 bone marrow biopsies of multiple myeloma patients where NY-ESO-1 protein was found to be expressed by immunohistochemistry in 9.7% of samples. Adoptively transferred NY-ESO-1-specific re-directed T cells protected mice against challenge with endogenously NY-ESO-1-positive myeloma cells in a xenograft model. In conclusion, re-directed effector-and central memory T cells specifically recognized NY-ESO-1(157-165)/HLA-A*02:01-positive cells resulting in antigen-specific functionality in vitro and in vivo. Gene Therapy (2013) 20, 386-395; doi: 10.1038/gt.2012.48; published online 28 June 2012
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