International Journal of Clinical Case Reports 2024, Vol.14, No.3, 132-143 http://medscipublisher.com/index.php/ijccr 135 3.3 Vaccine delivery systems Effective delivery systems are essential for the success of peptide-based vaccines. Traditional delivery methods, such as subcutaneous or intramuscular injections, often require the use of adjuvants to enhance the immune response. However, newer delivery systems are being developed to improve the stability, bioavailability, and immunogenicity of peptide vaccines (He et al., 2018; Zamani et al., 2020). Nanoparticles, liposomes, and other nanomaterials are being investigated as delivery vehicles for peptide vaccines. These systems can protect peptides from degradation, facilitate their uptake by APCs, and provide sustained release of the antigen. For example, liposomal formulations containing long multi-epitope peptides have shown promise in preclinical models by inducing strong CD4+ and CD8+ T cell responses and reducing tumor growth6. Additionally, the use of delivery systems that target specific tissues or cells can enhance the precision and effectiveness of the vaccine (He et al., 2018; Stephens et al., 2021). 3.4 Interaction with tumor microenvironment The tumor microenvironment (TME) plays a significant role in the efficacy of peptide-based vaccines. The TME is often immunosuppressive, with various factors such as regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and immunosuppressive cytokines that inhibit the immune response. Overcoming this immunosuppressive environment is crucial for the success of cancer vaccines (Tardón et al., 2019; Buonaguro and Tagliamonte, 2023). Strategies to modulate the TME include the use of combination therapies that pair peptide vaccines with immune checkpoint inhibitors, such as anti-PD-1 or anti-CTLA-4 antibodies. These inhibitors can block the pathways that suppress T cell activity, thereby enhancing the immune response to the vaccine. Additionally, the use of adjuvants that activate innate immune responses can help to reprogram the TME to be more supportive of anti-tumor immunity (Parmiani et al., 2014; Bezu et al., 2018). Peptide-based vaccines for oral cancer leverage the body's immune system to target and destroy cancer cells. The success of these vaccines depends on the careful design and selection of peptides, effective delivery systems, and strategies to overcome the immunosuppressive tumor microenvironment. Ongoing research and clinical trials continue to refine these approaches, with the goal of improving the clinical outcomes for patients with oral cancer. 4 Preclinical Studies on Peptide-Based Vaccines for Oral Cancer 4.1 In vitro studies In vitro studies are crucial for understanding the fundamental mechanisms of peptide-based vaccines and their potential efficacy against oral cancer. These studies typically involve the use of cancer cell lines to evaluate the immunogenicity and cytotoxic effects of peptide vaccines. For instance, peptide vaccines designed to target tumor-associated antigens (TAAs) or tumor-specific antigens (TSAs) have shown promise in eliciting strong immune responses. The peptides are often modified to enhance their immunogenicity, which can lead to a more robust activation of T cells (Parmiani et al., 2014; Liu et al., 2021; Abd-Aziz and Poh, 2022). One significant advantage of peptide-based vaccines is their ability to be synthesized easily and their minimal side effects when administered in vivo. This has been demonstrated in various cancer types, including oral cancer, where peptides derived from TAAs can successfully elicit CD8+and CD4+T cell-specific responses (Brinkman et al., 2004; Peres et al., 2015; Khong and Overwijk, 2016). The use of adjuvants in these vaccines is also critical, as they can significantly enhance the immune response by promoting the activation and maturation of dendritic cells, which are essential for T cell activation (Khong and Overwijk, 2016; Abd-Aziz and Poh, 2022). 4.2 Animal models Animal models play a pivotal role in preclinical studies by providing a more comprehensive understanding of the vaccine's efficacy and safety in a living organism. Studies using mouse models have shown that peptide-based vaccines can induce potent anti-tumor immune responses. For example, a study involving a nanoliposomal
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