Harnessing surface antigens shared by tumour cells and induced pluripotent stem cells could prevent the development of cancer in mice and elicit anti-tumor immune responses in both animal models and human blood samples, Chinese Academy of Sciences researchers found.

A study conducted by scientists from the National Center for Nanoscience and Technology, University of Chinese Academy of Sciences demonstrated that the membranes of induced pluripotent stem cells (iPM) contain a significant number of tumor-shared antigenic peptides. When used as antigens to train the immune system in various mouse models, iPM-based nanovaccine (iPM nanovax) effectively prevented the development of those tumors. Furthermore, in healthy human peripheral blood samples, iPM nanovax was shown to stimulate a strong immune response specific to the tumor-shared antigenic peptides. This approach holds promise as a universal tumor prophylactic vaccine for use in healthy populations. This study was published online in Nature Biomedical Engineering.

"To alleviate the burden of cancer, the development of tumor prophylactic vaccines is the long-sought goal for scientists and medical doctors. However, the genomic characteristics of non-virus-induced malignant tumor cells are highly diverse, and no universal tumor antigens (tumor-shared antigens) have been reported," said Professor ZHAO Ruifang . "To address this challenge, we took an innovative approach by capturing shared features of tumors from the perspective of tumor cell physiology to identify shared antigens. For example, when normal cells transformed into tumor cells, they acquired some traits of sustained proliferation, which are similar to those of induced pluripotent stem cells (iPSCs). We hypothesized that when cells transform into continuously proliferating cells, for example, tumor cells or iPSCs, the genes associated with traits like sustained proliferation drive the expression of a broad range of characteristic proteins on the cell membrane. This proteome can serve as a library of shared antigens reflecting tumor traits."

Prevention effect of the iPM nanovax

The research team first developed a prophylactic cancer nanovaccine based on iPM. In mouse models, the iPM nanovax was shown to activate B-cell and T-cell immune memory significantly and demonstrated remarkable antitumor immune protection in B16F0, MC38, 4T1, CT26, and 4T1 postoperative lung metastasis models.

The tumor-shared antigens for the antigenicity of iPM

To investigate what substances on the iPSC membranes triggered this antitumor-specific immune response, the project team developed a method to identify tumor-shared antigens on the cell membranes. They identified tumor-shared antigen peptides, which are associated with abnormal proliferation. These peptides possess broad-spectrum cancer prevention capabilities and can induce significant antigen-specific immune responses in peripheral blood mononuclear cells from healthy individuals. Furthermore, the research team also demonstrated that these tumor-shared antigens have good safety profiles and do not pose a risk of autoimmune reactions.

Overall, this strategy to identify the tumor-common antigens using the shared phenotype of unlimited cell proliferation bypasses the tedious process of identifying single antigens or antigen combinations, improving the efficiency of antigen identification and providing new ideas for the development of broad-spectrum cancer preventive vaccines.

Contact: ZHAO Ruifang

National Center for Nanoscience and Technology (NCNST)

E-mail: Zhaorf@nanoctr.cn

Schematic diagram of the design, preparation process, and mechanism of tumor preventive vaccines (Image by ZHAO Ruifang et al)