Publication

Effector memory and central memory NY-ESO-1-specific re-directed T cells for treatment of multiple myeloma

Journal Paper/Review - Jun 28, 2012

Units
PubMed
Doi

Citation
Schuberth P, Renner C, Fox B, Bifulco C, Tinguely M, Thiel M, Held G, Mischo A, Haile S, Haley D, Gautschi F, Wadle A, Jensen S, Jakka G, Petrausch U. Effector memory and central memory NY-ESO-1-specific re-directed T cells for treatment of multiple myeloma. Gene Ther 2012
Type
Journal Paper/Review (English)
Journal
Gene Ther 2012
Publication Date
Jun 28, 2012
Issn Electronic
1476-5462
Brief description/objective

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 IFNγ. 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 advance online publication, 28 June 2012; doi:10.1038/gt.2012.48.