Journal of Vaccine Research, 2025, Vol.15, No.1, 45-55 http://medscipublisher.com/index.php/jvr 51 because the tumor-surrounding environment can suppress immunity, immune checkpoints are activated, and there are regulatory cells that hinder the efficacy of vaccines (Saxena et al., 2021). Therefore, the proportion of effective vaccines in clinical trials is not high, and the improvement in the overall survival time of patients is limited, especially when treated with vaccines alone (Figure 2) (Garcia-Pardo et al., 2022; Chen et al., 2024). Figure 2 Antitumorimmunemechanismoftherapeuticcancervaccines (Adopted from Chen et al., 2024) Image caption: Tumor antigens are internalized bydendritic cells (DCs) following vaccination and then are processed within the DCs. These processed antigens are subsequently presented on the surface of DCs in association with major histocompatibility complex classI (MHC-I) or classII (MHC-II) molecules; Antigen cross-presentation allows for activation of CD4+and CD8+T cells in the draining lymph node through the interaction between TCR and p-MHC; The activated CD8+T cells differentiates into cytotoxic T lymphocytes, which induce tumor cells apoptosis in the tumor site via different pathways; Activated CD4+T cells not only promote B Cells differentiate into plasma cell that generate antibodies to attack tumor cells, but also secrete cytokines to boost the antitumor effect of CD8+T cells (Adopted from Chen et al., 2024) To address the issue of weak immunity, new approaches should be adopted, such as adding effective adjuvants, using them together with immune checkpoint inhibitors, or customizing vaccine formulations containing specific neoantigens for patients (Garcia-Pardo et al., 2022; Fan et al., 2023; Chen et al., 2024). However, these methods make research and development more complex and costly. How to better apply them in clinical treatment is still under study. Ensuring safety while enhancing the efficacy of vaccines remains a major challenge in this field. 5.3 Technical, financial and ethical challenges in clinical application There are many technical difficulties in the development and clinical application of therapeutic vaccines for non-small cell lung cancer. For instance, advanced production technology and strict quality control are required. When using the neoantigen method, vaccines need to be customized for patients quickly (Kiousi et al., 2023). These technical requirements will slow down the research and development progress, restrict the mass production of vaccines, especially personalized vaccines, which need to be designed and validated separately for each patient (Fan et al., 2023; Chen et al., 2024). Financial and ethical issues are also crucial. The high costs of vaccine research and development, production and clinical trials make it unaffordable for many patients, raising doubts about whether such investment by the healthcare system is worthwhile (Kiousi et al., 2023; Chen et al., 2024). Ethical challenges include ensuring fair access to new therapies for all, managing patient expectations rationally, and addressing the risk of adverse reactions brought about by immunity, especially when antigens may have adverse effects on normal tissues (Saxena et al., 2021; Fan et al., 2023). Only by addressing these issues can therapeutic vaccines truly become a routine treatment for non-small cell lung cancer. 6 Emerging Strategies and Future Directions 6.1 Personalized vaccine design and neoantigen discovery technology With the help of technologies such as next-generation sequencing (NGS), the research and development speed of
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