Journal of Vaccine Research, 2025, Vol.15, No.1, 45-55 http://medscipublisher.com/index.php/jvr 47 to work" and dysfunctional, further weakening the immune response and deteriorating both the innate immune capacity of the human body and the immune capacity stimulated by vaccines (Conforti et al., 2021; Liu et al., 2021; Huang, 2024). Recent studies have discovered new "dodging tricks", such as tumor cells transferring problematic mitochondria to til cells, causing metabolic problems and functional impairment of til cells, which is related to the poor effect of immunotherapy (Ikeda et al., 2025). In addition, non-coding rna and exosome PD-L1 can "paralyze" CD8+T cells and also make tumors resistant to chemotherapy and immunotherapy, causing immunosuppression (Hong et al., 2020; Liu et al., 2021). The various evasion methods of tumors indicate that in order to overcome the immunosuppressive environment around tumors and improve the therapeutic effect of non-small cell lung cancer, multiple methods need to be combined to design more innovative vaccines (Anichini et al., 2020; Yu et al., 2025). 3 Therapeutic Vaccines for Non-Small Cell Lung Cancer 3.1 Mechanism and representative research on peptide, protein-based and dendritic cell Vaccines The non-small cell lung cancer vaccine is made of polypeptides and proteins. It delivers tumor-associated substances (TAAs) or tumor-specific substances (tas) to the human immune system, with the aim of activating T lymphocytes capable of eliminating cancer cells and enabling them to attack cancer cells. Multiepitope peptide vaccines targeting MAGE-A3 or WT1 have already enabled the body to generate T-cell responses that can specifically recognize antigens. However, due to the complexity and variability of tumor conditions and the need to avoid attacks from the immune system, the actual therapeutic effects of these vaccines are not very satisfactory (Batool et al., 2021). The working principle of protein vaccines is similar to that of polypeptide vaccines, but they use larger antigen fragments, which might enable the immune system to recognize them more fully. Clinical trials show that these vaccines are generally safe and can also trigger an immune response in the human body. However, how to turn this immune response into a significant therapeutic effect remains a difficult problem (Oliveres et al., 2018; Garcia-Pardo et al., 2022; Wang et al., 2024). Dendritic cell (DC) vaccines utilize the cells in the human body that are most capable of delivering antigens. First, tumor antigens are "loaded" onto these cells in vitro, and then reinfused into the patient's body to activate naive T cells. Recent studies, including experiments using allogeneic plasma cell-like DC lines, have shown that DC vaccines can effectively activate CD8+T cells specifically fighting tumors in patients with non-small cell lung cancer, especially when used in combination with immune checkpoint inhibitors. Although DC vaccines can increase the number of T cells that fight tumors and enhance immune memory, their therapeutic effect is limited when used alone. Therefore, people are studying combination therapy methods and how to better select antigens (Garcia-Pardo et al., 2022; Hannani et al., 2023). 3.2 Research progress and challenges of nucleic acids and whole-cell vaccines Nucleic acid vaccines, especially those based on mRNA, are attracting increasing attention due to their fast development speed, flexible application, and the ability to encode multiple antigens. mRNA vaccines can be customized based on the mutation status of each patient's tumor, providing personalized regimens for the immunotherapy of non-small cell lung cancer (Kiousi et al., 2023; Wang et al., 2024). Early clinical trials are currently underway. Although the initial results suggest that the vaccine holds promise in terms of safety and triggering an immune response, there are still many difficulties in terms of transportation methods, stability, and how to induce a long-lasting and strong immune response in the body. DNA vaccines and viral vector vaccines are also under research. Some have already enabled the body to generate humoral immunity and cellular immunity, but there is still a long way to go before they can be actually applied in clinical practice. Whole-cell vaccines display multiple antigens to the human immune system by using irradiated tumor cells or cell fragments, which may address the issue of significant differences in tumors among individuals. This vaccine can simultaneously activate the innate immunity and adaptive immunity of the human body. However, because its ability to stimulate the immune response is not strong enough, it may also cause the body to develop tolerance to the immune response, so the actual effect is not ideal (Oliveres et al., 2018; Wang et al., 2024). In addition, the production process of whole-cell vaccines is very complicated and there is a lack of unified production standards,
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