Journal of Vaccine Research, 2025, Vol.15, No.1, 45-55 http://medscipublisher.com/index.php/jvr 48 which seriously hinders their application in large-scale clinical treatment. Even in the face of so many difficulties, whole-cell vaccines remain a key research area of concern for researchers, especially when used in combination with immune adjuvants or other immunotherapy methods to enhance the therapeutic effect. 3.3 Advantages and limitations of different vaccine platforms in inducing specific immune responses Peptide and protein vaccines are highly targeted, relatively easy to produce, can precisely trigger immune responses, and are less likely to cause side effects. However, their effects are often limited by HLA, antigens are prone to decomposition, and may also cause the body to develop immune tolerance, especially when the tumor has already suppressed the immune function (Batool et al., 2021; Wang et al., 2024). The DC vaccine has a strong ability to deliver antigens and can effectively activate T cells. However, its production process is troublesome and the cost is high. Its effect is average when used alone to treat non-small cell lung cancer (Garcia-Pardo et al., 2022; Hannani et al., 2023). Nucleic acid vaccines, especially mRNA vaccines, have fast research and development, large production volumes, and can be customized. They can encode multiple antigens and are particularly suitable for personalized immunotherapy. However, it also has drawbacks, such as being difficult to deliver to the body, requiring multiple vaccinations, and in an environment where tumors suppress immunity, it is hard to ensure sufficient immune efficacy (Kiousi et al., 2023). Whole-cell vaccines can display a large number of antigens and may solve the problem of significant tumor differences, but they have problems such as difficulty in standardization, weak immune stimulation ability, and the induction of immune tolerance (Oliveres et al., 2018; Wang et al., 2024). Overall, each vaccine has its own strengths and weaknesses. This requires continuous innovation and the combination of different methods in order to achieve better therapeutic effects for non-small cell lung cancer (Garcia-Pardo et al., 2022; Chen et al., 2024) 4 Clinical Evidence and Trials 4.1 Review of key clinical trials of therapeutic vaccines In recent years, an increasing number of clinical trials of therapeutic vaccines for non-small cell lung cancer have been carried out, and currently, the number of registered trials has exceeded 100. Early research mainly focused on peptide vaccines, protein vaccines, dendritic cell vaccines, nucleic acid vaccines and whole-cell vaccines (Gu et al., 2022; Baka et al., 2024; Chen et al., 2024; Wang et al., 2024). Peptide and protein vaccines targeting telomerase (GV1001) and indoleamine 2,3-dioxygenase (IDO) have not only been proven safe for use but also can stimulate the immune response in the human body. In some patients, these vaccines prolonged the duration of the immune response and also enabled the patients to live longer (Brunsvig et al., 2011; Kjeldsen et al., 2018). Dendritic cell vaccines, including those targeting tumor neoantigens, can also trigger a strong and long-lasting T-cell immune response in the human body. Some patients thus acquired long-term immune memory and their conditions were controlled (Figure 1) (Ingels et al., 2024; Liu, 2024). Personalized neoantigen vaccines like NEO-PV-01 have also performed well in terms of safety and immune stimulation. Studies have shown that they can expand the immune response range and activate T cells specifically against tumors (Awad et al., 2022). However, most of these clinical trials were not large in scale, and many did not adopt randomization and blinding designs. Therefore, there is still very little data that can fully prove the efficacy of the vaccine (Gu et al., 2022; Wang et al., 2024). Most of the studies were conducted in North America and Europe, and the research subjects were mostly patients with advanced (stage III-IV) non-small cell lung cancer. Although some candidate vaccines have shown good results in early trials, problems such as the complexity and variability of tumor antigens and their tendency to evade immune attacks still exist. Moreover, there are currently no large-scale randomized controlled studies to determine whether these vaccines can actually extend the lifespan of patients (Baka et al., 2024; Chen et al., 2024). 4.2 Monotherapy and combination therapy When therapeutic vaccines are used alone, they are generally safe and can also induce an immune response against tumor antigens in the human body. However, when it comes to reducing tumors and prolonging patients' lives, the effect is not ideal (Brunsvig et al., 2011; Kjeldsen et al., 2018; Chen et al., 2024). For instance, peptide
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