Natural killer cell engineering for cellular therapy of cancer

Tissue Antigens. 2011 Dec;78(6):409-15. doi: 10.1111/j.1399-0039.2011.01796.x.

Abstract

Natural killer (NK) cells can kill transformed cells and represent a promising tool for the treatment of cancer. Their function is governed by a balance of stimulatory and inhibitory signals triggered by surface receptors. Advances in NK cell therapy require the development of dependable methods for obtaining an adequate number of effector cells; additional activation or genetic modification may further increase their anticancer capacity. A method for NK cell expansion used in our laboratory relies on a genetically modified form of the K562 myeloid leukemia cell line, engineered to express a membrane-bound form of interleukin-15 and the ligand for the costimulatory molecule 4-1BB (CD137). Expanded NK cells can be transduced with genes encoding chimeric antigen receptors that stimulate tumor cell-specific cytotoxicity. These methods for NK cell expansion and genetic modification have been adapted to large-scale, clinical-grade, Current Good Manufacturing Practice conditions and support two active clinical trials. Summarized are current efforts for NK cell immunotherapy for cancer and future perspectives.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-1BB Ligand / biosynthesis
  • 4-1BB Ligand / genetics
  • 4-1BB Ligand / immunology
  • Cell Engineering / methods*
  • Humans
  • Immunotherapy, Adoptive*
  • Interleukin-15 / biosynthesis
  • Interleukin-15 / genetics
  • Interleukin-15 / immunology
  • K562 Cells
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / transplantation*
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / therapy*

Substances

  • 4-1BB Ligand
  • IL15 protein, human
  • Interleukin-15
  • TNFSF9 protein, human