Antigen amplification strategy shows promise for more precise next-generation immunotherapies

Tumor immunotherapies, especially those leveraging T-cells to identify and eliminate cancer cells, represent a major breakthrough in cancer treatment. However, many tumor-associated antigens are not expressed at a high enough density on the cancer cell surface to effectively activate T-cells, and these antigens are often present at low levels in normal tissues, leading to poor treatment specificity and potential off-target toxic side effects.

In a study published in Nature, a research team led by Prof. Han Shuo from the Center for Excellence in Molecular Cell Science (Shanghai Institute of Biochemistry and Cell Biology) of the Chinese Academy of Sciences applied proximity labeling to immunomodulation for the first time and developed a novel cell-surface protein engineering strategy named Proximity Amplification and Tagging of Cytotoxic Haptens (PATCH), solving the key bottlenecks in immunotherapy.

Proximity labeling, a technique typically used for detecting the spatial relationships of proteins, is an innovative approach from the perspective of chemical biology. Researchers reimagined proximity labeling as a functional modulation tool. Their goal was to directly amplify targeting signals on the tumor cell surface, thereby marking the cells that need to be attacked by the immune system.

In the newly developed PATCH strategy, an engineered nanozyme (PCN) was first delivered to the surface of tumor cells, and th

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