Chinese researchers have developed an innovative "intratumoral vaccine" molecule that prevents cancer cells from suppressing immune function while redirecting the body's existing immune memory to attack tumors, offering a new approach to cancer treatment.
Scientists from Shenzhen Bay Laboratory and Peking University reported the findings in a study published online in the journal Nature on Thursday (January 8).
Although immune checkpoint blockade therapy has revolutionized cancer treatment by enhancing the immune system's ability to target tumors, it is still ineffective for many patients.
One of the main reasons is the low mutational load and the lack of neoantigens, so that malignant cells in many patients escape the surveillance of the immune system.
The research team then tapped into a relatively underexplored immune resource: "bystander T cells." These T cells are formed in response to previous infections, such as cytomegalovirus (CMV), and although they remain dormant, they retain immunological memory in most adults.
Researchers hypothesized that if tumors could be made to display CMV antigens, these abundant memory T cells could be mobilized to fight the cancer.
To achieve this, the team designed a synthetic molecule called an "intratumoral vaccination chimera" (iVAC). This dual-purpose molecule permanently targets and degrades the PD-L1 protein on tumor cells, effectively releasing the immune system's brakes, while simultaneously delivering CMV antigen epitopes.
By marking tumors with the virus's signature, iVAC redirects the body's reservoir of anti-CMV T cells to recognize and destroy cancer cells.
In tests on both mouse models and patient-derived tumors, iVAC successfully activated T cells and demonstrated potent antitumor activity. These results demonstrate the potential of harnessing the immune system's memory against common viruses for cancer therapy.
The researchers are currently developing translational molecules based on the mechanism revealed in the study and aim to bring this technology to clinical trials in the future, said Chen Peng, a senior researcher at Shenzhen Bay Laboratory.
