Harnessing surface antigens shared by tumor 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, a new study showed. This study, conducted by researchers from the National Center for Nanoscience and Technology of the Chinese Academy of Sciences (CAS) and the University of Chinese Academy of Sciences of CAS, was published online in Nature Biomedical Engineering.
Researchers 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. 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.
"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 Prof. ZHAO Ruifang from National Center for Nanoscience and Technology.
"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 like 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," added Prof. ZHAO.
To prove the prevention effect of the iPM nanovax, researchers 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.
To investigate what substances on the iPSC membranes triggered this antitumor-specific immune response, researchers developed a method to identify tumor-shared antigens on the cell membranes. They identified tumor-shared antigen peptides associated with abnormal proliferation. These peptides possessed broad-spectrum cancer prevention capabilities and could induce significant antigen-specific immune responses in peripheral blood mononuclear cells from healthy individuals. These tumor-shared antigens were demonstrated to have good safety profiles and do not pose a risk of autoimmune reactions.
The 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, and improves the efficiency of antigen identification, providing new ideas for the development of broad-spectrum cancer preventive vaccines.
Source: Chinese Academy of Sciences
Editor: GAO Yuan
