Natural killer cell membrane manipulation for augmented immune synapse and anticancer efficacy

Area of Science:

• Immunology
• Biomaterials Science
• Cancer Research

Background:

• Natural killer (NK) cells possess inherent anti-tumor properties, making them promising for cancer immunotherapy.
• Genetic engineering, such as chimeric antigen receptor (CAR)-NK cells, enhances NK cell specificity and activation against tumors.
• Biomaterial-assisted surface engineering provides a genome-independent method to customize NK cell function.

Purpose of the Study:

• To review advances in NK cell-based cancer immunotherapy.
• To highlight the potential of native NK cells and CAR-NK cell platforms.
• To discuss emerging biomaterial-assisted surface engineering strategies for enhancing NK cell-mediated anti-tumor responses.

Main Methods:

• Review of preclinical and clinical studies on NK cell immunotherapy.
• Analysis of genetic engineering approaches, including CAR-NK cells.
• Examination of biomaterial-assisted surface engineering techniques (e.g., covalent conjugation, metabolic glycoengineering, click chemistry, hydrophobic insertion).

Main Results:

• Engineered NK cells, particularly CAR-NK cells, show significant antitumor efficacy.
• Biomaterial strategies enable precise presentation of targeting ligands and immunomodulatory molecules on NK cell surfaces.
• Surface engineering supports programmable cell-tumor interactions while preserving NK cell cytotoxicity.

Conclusions:

• Biomaterial-assisted surface engineering is a flexible, modular, and practical complementary strategy to genetic engineering for NK cell-based cancer therapies.
• These material-guided approaches, alongside genetic strategies, are expanding the toolkit for next-generation cancer immunotherapies.
• Further research is needed to address challenges like *in vivo* persistence and effector response control.