# Immunotherapy of chimeric antigen receptor NK cells: status and its promising future

## TL;DR

CAR NK cells are a promising alternative to CAR T cells for cancer therapy, especially for solid tumors, due to their unique immune properties and safety profile.

## Contribution

This review synthesizes current research on CAR NK cells to highlight their potential and challenges in cancer immunotherapy.

## Key findings

- CAR T-cell therapy is less effective against solid tumors due to production and infiltration challenges.
- CAR NK cells offer advantages like potent cytotoxicity and better safety, making them suitable for solid tumor treatment.
- Technical challenges like NK cell persistence and preparation limit their clinical adoption.

## Abstract

Chimeric antigen receptors (CARs) are genetically engineered fusion proteins composed of extracellular antigen-recognition domains and multiple intracellular signaling domains. Although CAR T-cell immunotherapy has achieved significant advancements in treating hematologic malignancies, its application against solid tumors remains less successful. Key challenges—including production complexities, the scarcity of tumor-specific antigens, and limitations in cell trafficking and tumor infiltration—continue to impede therapeutic efficacy. Natural killer (NK) cells, essential innate immune lymphocytes, play a critical role in targeting malignant cells. Their unique antigen-recognition mechanisms, potent cytotoxicity, and favorable clinical safety profile position CAR NK cells as a promising alternative for targeted cancer therapy, especially for solid tumors. However, the transient persistence of NK cells in vivo and the technical challenges associated with their preparation currently limit the broader clinical adoption of this approach. This review examines the advantages of CAR NK cells immunotherapy and synthesizes current domestic and international research to advance the understanding of CAR NK cells therapeutics.