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The emerging role of off-the-shelf engineered natural killer cells in targeted cancer immunotherapy

Kellsye P Fabian1, James W Hodge1

  • 1Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Room 8B09, Bethesda, MD 20892, USA.

Molecular Therapy Oncolytics
|November 11, 2021
PubMed

Insights

Natural killer (NK) cell therapy, specifically using the NK-92 cell line engineered with chimeric antigen receptors (CARs), shows promise for cancer treatment. These CAR NK-92 cells are safe and effective in preclinical and early clinical studies.

Area of Science:

  • Immunology
  • Cell Biology
  • Oncology

Background:

  • Natural killer (NK) cells are crucial innate immune cells for identifying and eliminating infected or cancerous cells.
  • NK cell-based therapies are being developed for cancer treatment due to their tumor surveillance capabilities.
  • The NK-92 cell line offers a versatile platform for developing off-the-shelf cell therapies without HLA matching requirements.

Purpose of the Study:

  • To review recent advancements in the research and clinical applications of chimeric antigen receptor (CAR)-engineered NK-92 cell therapy.
  • To highlight the potential of CAR NK-92 cells as a next-generation cancer immunotherapy.
  • To discuss the safety and efficacy of CAR NK-92 cells in preclinical and clinical settings.

Main Methods:

  • Modification of the NK-92 cell line to express high-affinity CD16 receptors and/or chimeric antigen receptors (CARs).
  • Evaluation of CAR NK-92 cell activity through in vitro and in vivo preclinical studies.
  • Analysis of preliminary Phase 1 clinical trial data for safety and tolerability.

Main Results:

  • CAR-engineered NK-92 cells demonstrate significant antitumor activity in preclinical models.
  • The NK-92 platform allows for CAR engineering without the need for human leukocyte antigen (HLA) matching.
  • Preliminary Phase 1 clinical data suggest that CAR NK-92 cells can be safely administered to patients.

Conclusions:

  • CAR NK-92 cells represent a promising off-the-shelf cell therapy for cancer treatment.
  • Further clinical development is warranted based on robust preclinical data and initial safety findings.
  • This novel cell immunotherapy holds potential for advancing cancer treatment strategies.
Keywords:
CAR NKNK-92adoptive cell therapyhaNKhigh-affinity NKnatural killer cellst-haNKtargeted high-affinity NK

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