Design and Implementation of NK Cell-Based Immunotherapy to Overcome the Solid Tumor Microenvironment

Area of Science:

• Immunology
• Cancer Therapy
• Cellular Engineering

Background:

• Natural killer (NK) cells are innate immune cells with cytotoxic capabilities.
• NK cells offer advantages over other cell therapies, including reduced risk of graft-versus-host disease (GvHD) and cytokine release syndrome (CRS).
• Current NK cell therapies face challenges in overcoming the immunosuppressive tumor microenvironment (TME) of solid tumors.

Purpose of the Study:

• To review strategies for enhancing NK cell-based therapies against solid tumors.
• To outline mechanisms by which TME components suppress NK cell activity.
• To describe engineering approaches that improve NK cell efficacy in the TME.

Main Methods:

• Review of genetic and non-genetic engineering approaches for NK cell modification.
• Analysis of strategies to enhance NK cell cytotoxicity and resistance to TME factors.
• Discussion of methods to improve NK cell persistence within the TME.

Main Results:

• Various engineering strategies can enhance NK cell receptor-mediated cytotoxicity.
• Approaches exist to improve NK cell resistance to immunosuppressive TME effects.
• Methods for prolonging NK cell persistence in the TME are under development.

Conclusions:

• Overcoming TME-mediated suppression is critical for successful NK cell therapy in solid tumors.
• Genetic and non-genetic engineering holds potential for creating more effective NK cell therapeutics.
• Enhanced NK cell strategies promise more robust treatments for solid tumor patients.