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Tumor vaccines that activate the autoimmune system to eliminate tumor cells are a type of cancer immunotherapy Effective method. Traditional tumor vaccines are divided into two categories: tumor-associated antigen vaccines and personalized neoantigen vaccines. Although these traditional tumor vaccines have achieved remarkable results in clinical trials in recent years, they still face problems such as tumor heterogeneity, limited antigen selection, insufficient antigen presentation, and slow immune response, which lead to poor universality and response rate. In contrast, pathogen-specific immunity acquired through infection or vaccination can rapidly generate more effective and durable immune responses upon re-encountering the same antigen. The receptor binding domain (RBD) of SARS-CoV-2 is highly immunogenic, and the global COVID-19 vaccination has enabled a large number of people to establish pre-existing RBD-specific immunity. Recently, a paper titled "A Universal Therapeutic Vaccine Leveraging Autologous Pre-Existing Immunity to Eliminate in Situ Uniformly Engineered Heterogeneous Tumor Cells" published in Advanced Materials introduced a new type of universal therapeutic tumor vaccine, which uses adeno-associated virus (AAV) vectors to genetically engineer a variety of tumor cells to overexpress and efficiently present the highly immunogenic SARS-CoV-2 receptor binding domain (RBD), and awaken and enhance the pre-existing immune response against RBD, thereby achieving in situ elimination of a variety of tumor cells (as shown in Figure 1). The results of the study showed that the vaccine can significantly inhibit tumor growth, induce antigen spread, and stimulate a broad range of tumor-specific cellular immune responses, providing new ideas for overcoming tumor heterogeneity and the limitations of personalized medicine. The researchers chose AAV as a vector, and took advantage of its high safety, broad tissue tropism, and persistent transgenic expression ability to design a vaccine that enables tumor cells to overexpress and efficiently present RBD. Through structural optimization, a gene sequence was designed that can simultaneously express trimeric RBD on the cell membrane and release RBD-encapsulated virus-like particles (eVLPs) to awaken and enhance RBD-specific immunity. ShRNAs that can silence PD-L1 and SUSD6 were embedded in the AAV vector to enhance the tumor killing ability mediated by cytotoxic T cells, and AAV and CpG1018 adjuvants were encapsulated in thermosensitive hydrogels to achieve local administration, ensuring continuous expression of antigens and immune activation while reducing systemic side effects.
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AAV-DJ achieved an infection efficiency of over 99% in B16F10, 4T1, and CT26 tumor cells. The STMHR sequence successfully achieved transmembrane and secretory expression, while shRNA effectively silenced the PD-L1 and SUSD6 genes. In mice pre-vaccinated with inactivated vaccines or mRNA vaccines, the RBD-specific antibody titer was significantly increased and the cellular immune response was enhanced after treatment with the vaccine. In a variety of tumor models, the vaccine significantly inhibited tumor growth, prolonged survival, and some mice even achieved complete remission. Antigen diffusion was induced during treatment, stimulating immune memory against RBD and original tumor cells. In addition, the vaccine showed good therapeutic effects in mouse models with different HLA genes, indicating its potential universality.
Figure 1. Schematic diagram of a universal therapeutic vaccine that utilizes autoimmunity to eliminate multiple in situ tumor cells In summary, the AAV-based universal therapeutic vaccine developed in this study can efficiently and specifically eliminate genetically modified tumor cells by awakening and enhancing pre-existing immune responses. The vaccine enhances anti-tumor immune responses by improving antigen presentation, increasing membrane antigen expression, and inducing antigen diffusion. It has shown good anti-tumor effects and safety in a variety of tumor models, and is expected to break through HLA restrictions and provide a new universal strategy for cancer immunotherapy.
Tumor vaccines that activate the autoimmune system to eliminate tumor cells are a type of cancer immunotherapy Effective method.
