Next generation natural killer cells for cancer immunotherapy: the promise of genetic engineering

Curr Opin Immunol. 2018 Apr:51:146-153. doi: 10.1016/j.coi.2018.03.013. Epub 2018 Mar 30.


Recent advances in the field of cellular therapy have focused on autologous T cells engineered to express a chimeric antigen receptor (CAR) against tumor antigens. Remarkable responses have been observed in patients receiving autologous CD19-redirected T cells for the treatment of B-lymphoid malignancies. However, the generation of autologous products for each patient is logistically challenging and expensive. Extensive research efforts are ongoing to generate an off-the-shelf cellular product for the treatment of cancer patients. Natural killer (NK) cells are attractive contenders since they have potent anti-tumor activity, and their safety in the allogeneic setting expands the cell sources for NK cell therapy beyond an autologous one. In this review, we discuss advantages and limitations of NK cellular therapy, and novel genetic engineering strategies that may be applied to overcome some of the limitations. Next-generation engineered NK cells are showing great promise in the preclinical setting and it is likely that in the next few years CAR-engineered NK cells will be incorporated into the current armamentarium of cell-based cancer therapeutics.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • Biomarkers, Tumor
  • Cell- and Tissue-Based Therapy
  • Cytotoxicity, Immunologic
  • Genetic Engineering
  • Humans
  • Immunologic Surveillance
  • Immunotherapy, Adoptive* / methods
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Neoplasms / immunology*
  • Neoplasms / therapy*
  • Receptors, Chimeric Antigen / genetics
  • Receptors, Chimeric Antigen / metabolism


  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Receptors, Chimeric Antigen