A team of Chinese scientists has recently developed a new protein targeted degradation technology, which delivers a novel molecule called "intratumoral vaccine chimera" (iVAC) into tumor cells. This not only adds an "identity tag" to "invisible" tumor cells, making them visible, but also activates immune responses, providing a new path to overcome the medical challenge of cancer immune tolerance. This breakthrough was published online on the 8th in Nature. The reviewer of Nature praised this achievement as an "encouraging discovery that provides an important theoretical foundation for the development of new therapeutic methods". Under normal circumstances, the immune system can recognize and eliminate tumor cells in the tumor microenvironment. However, in order to survive and proliferate, tumor cells adopt various strategies to suppress the multi-level response of the human immune system, resulting in the inability of the immune system to effectively kill tumor cells and achieve immune escape. Tumor immunotherapy is a treatment strategy that restarts and maintains the tumor immune cycle through various means, restores the body's normal anti-tumor immune response, and controls and clears tumors. However, in clinical practice, there are still many patients who do not respond to immunotherapy, due to the fact that tumor cells have learned the "invisibility technique". Researchers have introduced that some tumor cells can quietly escape the radar of the immune system, as if wearing a "invisibility cloak". Faced with tumor cells that lack "identity tags" and blend in with normal cells, traditional immunotherapy is like a skilled archer trapped in thick fog, unable to find the correct target, and even face-to-face, unable to recognize enemies and friends, resulting in treatment failure. The team led by Chen Peng from the School of Chemistry and Molecular Engineering at Peking University, together with the team led by Xi Jianzhong, Vice Dean of the School of Future Technology, and the team from the Shenzhen Bay Laboratory, have developed a new molecule iVAC through protein engineering. It can enter tumor cells without relying on specific "door locks" on the cell surface, and destroy the PD-L1 protein that can inhibit the activation of immune cells in the body. At the same time, this multifunctional molecule also carries antigens carefully selected by the team, which are then "reprogrammed" within tumor cells to produce antigen active fragments with immune response activity, which are then presented on the surface of tumor cells and become their "identity tags". Compared to traditional immune checkpoint blockade therapy, iVAC has shown significant anti-tumor effects. It not only helps the immune system 'see' tumor cells, but also efficiently activates effector T cells that can clear virus-infected tumor cells, thereby forming a positive feedback loop of immune response and effectively inhibiting tumor recurrence. ”Xi Jianzhong said. It is said that the molecule can also shuttle and infiltrate in dense solid tumors, which is another major reason for its good anti-tumor effect. Xi Jianzhong stated that this achievement is due to the collaborative research and development of multidisciplinary cutting-edge methods such as modular design of drug molecules and efficacy evaluation based on humanized micro tumor models. At present, we are actively promoting clinical translation. In the future, personalized and universal cancer vaccines can be rapidly iterated for different patients, bringing new treatment hope to cancer patients