Chinese researchers have developed an innovative intratumoral vaccine molecule that prevents cancer cells from suppressing immune function while redirecting the body’s pre-existing immune memory to attack tumours, offering a novel approach to cancer treatment.

Scientists from Shenzhen Bay Laboratory and Peking University reported the findings in a study published online in the journal Nature.

Although immune checkpoint blockade therapy has transformed cancer treatment by enhancing the immune system’s ability to target tumours, it remains ineffective for many patients.

Researchers said a primary reason is that, due to low mutational burden and a consequent lack of neoantigens, malignant cells in many patients evade recognition by the immune system.

The research team turned to a largely untapped immune resource known as bystander T cells. Generated in response to prior infections such as cytomegalovirus, these T cells remain dormant but retain immunological memory in most adults.

The scientists proposed that if tumours could be made to display cytomegalovirus antigens, these abundant memory T cells could be mobilised against cancer.

To achieve this, the team designed a synthetic molecule known as an intratumoral vaccination chimera. This dual-function molecule irreversibly targets and degrades the PD-L1 protein on tumour cells, effectively releasing the immune system’s brakes, while also delivering a cytomegalovirus antigen epitope.

By marking tumours with this viral signature, the molecule redirects the body’s reservoir of anti-cytomegalovirus T cells to recognise and eliminate cancer cells.

In both mouse models and patient-derived tumour clusters, the molecule successfully activated T cells and demonstrated strong anti-tumour activity. The findings highlight the potential of harnessing immune memory against common viruses for cancer therapy.

The researchers are now developing translational molecules based on this mechanism and aim to advance the technology towards future clinical trials, said Chen Peng, a senior investigator at Shenzhen Bay Laboratory.