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Improving efficacy of cancer immunotherapy by genetic modification of natural killer cells

Rachel A Burga1, Tuongvan Nguyen2, Jane Zulovich2

  • 1Institute for Biomedical Sciences, The George Washington University, Washington, DC, USA; Children's National Health System, Washington, DC, USA.

Cytotherapy
|July 17, 2016
PubMed

Insights

Natural killer (NK) cells offer promising adoptive cell therapy due to their rapid cytotoxic abilities. Genetic modifications enhance NK cell function, overcoming tumor and viral evasion for improved cancer immunotherapy.

Area of Science:

  • Immunology
  • Cell Biology
  • Cancer Research

Background:

  • Natural killer (NK) cells are crucial innate immune cells with cytotoxic and cytokine-producing capabilities.
  • Their ability to rapidly lyse target cells without prior sensitization makes them ideal for adoptive cell therapy.
  • Tumors and viruses utilize evasion strategies to escape NK cell-mediated destruction, posing challenges for immunotherapy.

Purpose of the Study:

  • To review recent advancements in genetically modifying NK cells.
  • To explore strategies for enhancing NK cell function for improved immunotherapy.
  • To summarize the application of engineered NK cells in cellular immunotherapy.

Main Methods:

  • Genetic modification techniques to enhance NK cell properties.
  • Introduction of chemokine, high-affinity Fc receptors, and chimeric antigen receptors.
  • Incorporation of suicide genes and forced expression of cytokines like IL-2 and IL-15.

Main Results:

  • Preclinical studies demonstrate enhanced NK cell homing, cytolytic activity, and in vivo persistence.
  • Genetic engineering improves the safety profile of NK cell-based therapies.
  • Engineered NK cells show increased effectiveness against viral infections and malignancies.

Conclusions:

  • Genetic manipulation is a powerful tool to optimize NK cell-based immunotherapies.
  • Overcoming NK cell evasion strategies is key to fully exploiting their therapeutic potential.
  • Advances in NK cell engineering pave the way for novel cellular immunotherapeutic strategies against cancer and viral diseases.
Keywords:
gene transferimmunotherapynatural killer cells

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