There are a large number of gene mutations in tumor cells, some of which produce mutated peptides that have the potential to activate immune responses, called tumor antigens. As a kind of personalized tumor immunotherapy, tumor vaccine can activate tumor antigen-specific effector T cells by presenting tumor antigens to the immune system, so as to realize the immune recognition and killing of tumor cells. However, the immunogenicity of tumor antigens alone is low, and needs to be enhanced by the immune adjuvants and nanocarriers to activate an effective antitumor immune response. At present, the development trend of tumor nanovaccines is to develop nanocarriers that can also function as adjuvants themselves, there reducing the additional components and synthesis processes.
Based on the concept of integration of nanocarriers and adjuvants, inspired by the natural phenomenon that the body recognizes bacteria and generates immunity, Profs. Nie Guangjun, ZHAO Xiao and ZHAO Ruifang from the National Center for Nanoscience and Technology (NCNST) of the Chinese Academy of Sciences (CAS), have been committed to the development of tumor nanovaccines based on bacterial membrane materials for a long time. In the previous study, with the help of genetic engineering technology and polypeptide molecular glue technology, an individualized tumor nanovaccine platform based on bacterial outer membrane vesicles (OMVs) was constructed, which could rapidly display a variety of tumor antigens and realize the “Plug-and-Display” of tumor vaccine (Nat. Commun. 2021, 12(1): 2041). In addition, using heterozygous membrane nanotechnology, bacterial cytoplasmic membrane and tumor cell membrane were fused to cover the surface of the nanoparticles to construct a heterozygous membrane tumor nanovaccine (Sci. Transl. Med. 2021, 13: eabc2816).
On the basis of previous works, the technical details of the two tumor nanovaccines based bacterial membrane with different technical routes were summarized in detail, which were published in Nature Protocols recently. Meanwhile, the vaccine characterization, immune effect and antitumor effect evaluation methods in various tumor models were summarized. In the OMV-based “Plug-and-Display” tumor nanovaccines, the main bacterial component is the outer membrane of bacteria, which can effectively activate the TLR2/4/5 signaling pathways. The main technical feature is that known tumor antigens can be quickly linked and displayed on the surface of OMVs, which can be applied to customized tumor vaccines in the future when the tumor antigen information can be easily obtained. In the heterozygous membrane tumor nanovaccines, the main bacterial component is the bacterial cytoplasmic membrane, which can effectively activate the TLR1/2/6 signaling pathways. The main technical feature is that it can use and present the real tumor antigens on tumor cell membrane, which can be applied to individualized tumor vaccines in the future when it is difficult to obtain tumor antigen information.
In conclusion, based on the previous work, the team systematically summarized the technical characteristics, construction process and evaluation system of two kinds of tumor nanovaccines based on bacterial membrane materials (OMV-based “Plug-and-Display” tumor nanovaccines and heterozygous membrane tumor nanovaccines), which will greatly promote the future application of bacterial membrane materials.
Figure. Schematic diagram of technical routes for preparation of two kinds of tumor nanovaccines based on bacterial membrane materials. a, OMV-based “Plug-and-Display” tumor nanovaccines. b, heterozygous membrane tumor nanovaccines. (Image by NIE Guangjun et al)
National Center for Nanoscience and Technology