A collaboration work led by Associate Professor Qi ZHAO in the University of Macau (UM) Faculty of Health Sciences (FHS) and Professor Zhenfeng ZHANG in Guangzhou Medical University (GMU), have revealed that remodelling of tumor microenvironment by microwave ablation enhances the anti-tumor effect of chimeric antigen receptor (CAR) T cells. This technology can be used to improve the ability of the non-small cell lung cancer patient’s own immune system to fight the tumour. This is a major breakthrough in the treatment of solid tumors with CAR T cells. The research result has been published in the internationally renowned academic journal Nature Communications.
Adoptive cell therapy of CAR T cells is an innovative strategy for cancer treatment. Although CAR T cell therapy has been successfully approved as a clinical treatment of hematological malignancies, the therapeutic effect in solid tumours is not significant. Recent research shows that ALX protein is highly specifically expressed in non-small cell lung cancer (NSCLC), and it can be a target for CART cells to treat NSCLC. However, the complex immunosuppressive tumor microenvironment and the lack of tumour-specific targets are the main obstacles hindering ALX-CART cell therapy.
Microwave ablation, which uses electromagnetic waves to kill cells, has been widely used clinically to treat tumours. The joint research teams conducted a study on the combined treatment of microwave ablation and AXL-CAR-T cells on non-small cell lung cancer (NSCLC). The study found that microwave ablation enhanced the initiation, invasion, persistence, and tumour suppressive properties of AXL-CAR-T cells in NSCLC tumours by remodeling the tumor microenvironment. The mitochondrial oxidative metabolism of tumour-infiltrating CAR-T cells was increased. The team believes that the strategy of reshaping the tumour microenvironment is extremely important for enhancing the anti-tumour effect of CAR T cells. The results provide a theoretical basis for the synergistic therapy of MWA and CART cells. ALX-CART cell immunotherapy has the value of clinical transformation.
The corresponding authors of this study are Qi ZHAO (UM) and Zhenfeng ZHANG (GMU). FHS PhD student Shuo YANG and Shengyu FU made important contributions to this study. The study was funded by the Science and Technology Development Fund (FDCT), Macao SAR (file number: 0043/2021/A1and 0002/2021/AKP), National Key R&D Programme of China (file number: 2019YFA0904400), and UM (file number: MYRG2019-00069-FHS). The full-text version of the related paper can be viewed at: https://www.nature.com/articles/s41467-022-33968-5#Ack1.
Schematic diagram of combined anti-tumor effect of microwave ablation technology and CART cells.
Qi ZHAO