The application of CAR-T cell therapy against solid tumors is often hindered by the dense and rigid tumor extracellular matrix (ECM). While combining CAR-T with hyaluronidase (HAase) to reduce ECM is apparent, the efficacy is limited because of low accumulation and penetration efficiency of HAase inside the tumor tissue. Herein, the stimuli-responsive HAase-loaded nanogels (H-NGs) which are conjugated on the surface of CAR-T cells were designed for synergistically improving HAase accumulation, ECM degradation and CAR-T cell efficacy. The conjugation of H-NGs on the T cell surface was achieved through metabolic oligosaccharide engineering (MOE) in a semi-quantitatively controlled manner. Intravenous injection of H-NGs armed CAR-T cells resulted in more ECM degradation than co-injection of CAR-T cells and free H-NGs, leading to an 83.2% tumor inhibition rate and relieves tumor suppressive microenvironment in the Raji solid tumor model. Proteomic analysis of the harvested tumor tissues indicated that the combining of H-NGs and CAR-T cell collaboratively reduces cell adhesion and enhanced leukocyte transendothelial migration. Overall, this work simultaneously boosts the efficacy of hyaluronidase and CAR-T cells in combating solid tumor, which has broad application potential in cancer combination therapy.

Inspired by the reptiles’ grippy toes, researchers have developed an ultra-sticky material that adheres to tumors, delivering targeted chemotherapy for days.

Researchers at the University of Oxford and Nanyang Technological University, Singapore (NTU Singapore) have uncovered the mechanism by which cells identify and repair a highly toxic form of DNA damage that causes cancer, neurodegeneration, and premature ageing. The findings, published in Nucleic Acids Research, reveal how DNA-protein crosslinks (DPCs) – harmful DNA lesions induced by chemotherapy, formaldehyde, and UV exposure – are recognised and broken down by SPRTN, a key repair enzyme. The research team discovered a new region within SPRTN that enables it to selectively target DPC lesions, increasing its repair activity 67-fold while leaving surrounding structures unharmed.