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Chimeric antigen receptor natural killer cell therapy for solid tumors: mechanisms, clinical progress, and strategies

Yu Xiang1,2,3,4,5, Jiayi Dong1,2,3,4, Lijuan Shao1,2,3,4,5

  • 1Department of Immuno-Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangdong Pharmaceutical University, Guangzhou, China.

Experimental Biology and Medicine (Maywood, N.J.)
|January 5, 2026
PubMed

Insights

Chimeric antigen receptor natural killer (CAR-NK) cells show promise against solid tumors. Overcoming the tumor microenvironment and improving manufacturing are key for effective CAR-NK therapies.

Area of Science:

  • Immunology
  • Oncology
  • Biotechnology

Background:

  • Natural killer (NK) cells are crucial for innate immunity against infections and cancer.
  • Chimeric antigen receptor (CAR) technology enhances NK cell antitumor activity.
  • CAR-NK cells combine antigen-specific and innate cytotoxicity against tumors.

Purpose of the Study:

  • To review the clinical progress of CAR-NK cells in treating solid tumors.
  • To identify challenges and strategies for CAR-NK cell therapy in solid tumors.
  • To explore future research directions for CAR-NK cell deployment.

Main Methods:

  • Critical evaluation of clinical trial data for CAR-NK cell therapy in solid tumors.
  • Analysis of mechanisms to overcome the immunosuppressive tumor microenvironment (TME).
  • Review of allogeneic manufacturing complexities and engineering strategies for CAR-NK cells.

Main Results:

  • CAR-NK cells demonstrate dual cytotoxic effects against solid tumors.
  • Key challenges include the TME, allogeneic manufacturing, and CAR-NK cell persistence.
  • Need for robust Phase II/III data and standardized Good Manufacturing Practice (GMP) protocols is highlighted.

Conclusions:

  • CAR-NK cell therapy holds significant potential for solid tumor management.
  • Advancements in engineering and manufacturing are crucial for clinical success.
  • Further research and clinical validation are required for off-the-shelf allogeneic CAR-NK therapies.
Keywords:
chimeric antigen receptor natural killer cellsgene editingimmunotherapysolid tumorstumor microenvironment

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