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

Gene Ther. 2013 Apr;20(4):386-95. doi: 10.1038/gt.2012.48. Epub 2012 Jun 28.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / transplantation
  • Cell Line, Tumor
  • Genetic Therapy
  • Humans
  • Immunologic Memory
  • Immunotherapy*
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism
  • Mice
  • Multiple Myeloma / immunology
  • Multiple Myeloma / therapy*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / immunology*
  • Neoplasm Proteins / metabolism
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology*
  • Peptide Fragments / metabolism
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, CCR7 / genetics
  • Receptors, CCR7 / metabolism
  • Transduction, Genetic


  • Antigens, Neoplasm
  • CCR7 protein, human
  • IL2 protein, human
  • Interleukin-2
  • Neoplasm Proteins
  • Peptide Fragments
  • Receptors, Antigen, T-Cell
  • Receptors, CCR7
  • peptide NY-ESO-1 157-165
  • Interferon-gamma