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The prospect of genetically engineering natural killer cells for cancer immunotherapy

Angie Yu Ching Poon1, Ryohichi Sugimura1

  • 1School of Biomedical Science, University of Hong Kong, 21 Sassoon Rd, Hong Kong999077.

Biology Open
|November 29, 2022
PubMed

Insights

Engineered natural killer (NK) cells show promise in cancer immunotherapy. Genetic modification, particularly with chimeric antigen receptor (CAR)-NK cells derived from pluripotent stem cells, enhances tumor targeting and killing capacity for improved efficacy.

Area of Science:

  • Immunology
  • Oncology
  • Biotechnology

Background:

  • Natural killer (NK) cells are crucial for innate immunity against cancer.
  • Current NK cell immunotherapies face challenges with tumor-specific targeting and sustained anti-tumor activity in the tumor microenvironment.

Approach:

  • Genetic engineering strategies are reviewed to enhance NK cell functionality.
  • Approaches include increasing cytokine sensitivity, immune checkpoint evasion, and chimeric antigen receptor (CAR) transduction.
  • Human pluripotent stem cells (hPSCs) are explored as a scalable and genetically tractable source for engineered NK cells.

Key Points:

  • Engineered NK cells exhibit improved tumor-killing capacity and specificity.
  • CAR-NK cells have demonstrated efficacy against both hematologic and solid tumors in preclinical studies.
  • hPSC-derived NK cells offer a sustainable and expandable platform for immunotherapy.

Conclusions:

  • Genetic engineering, especially CAR transduction, significantly enhances NK cell-based cancer immunotherapy.
  • hPSC-derived CAR-NK cells represent a highly promising strategy for overcoming current limitations and advancing cancer treatment.
Keywords:
CAR-NKCancerCytokinesGenetic engineeringImmunotherapyNK cell

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