International Journal of Clinical Case Reports 2024, Vol.14, No.5, 230-241 http://medscipublisher.com/index.php/ijccr 236 life-threatening toxicities while ensuring that patients can continue to benefit from cancer vaccines and immunotherapies (Ramos-Casals et al., 2020). 5 Key Factors Affecting Efficacy 5.1 Patient characteristics and vaccine response Patient-specific factors such as age, immune status, and genetic background significantly influence the efficacy of cancer vaccines. For instance, older patients generally exhibit immunosenescence, characterized by a diminished immune response due to reduced numbers of naïve T cells and increased exhaustion of memory T cells. Despite these challenges, clinical trials have shown that immune checkpoint inhibitors (ICIs) combined with vaccines still provide comparable efficacy in both younger and older patients. A meta-analysis revealed that both younger (<65 years) and older patients (≥65 years) benefited from ICI-based treatments, though the overall survival (OS) benefit was slightly greater in older patients (Wu et al., 2019). Immune status also plays a critical role in vaccine response. Patients with compromised immune systems, such as those undergoing chemotherapy or suffering from autoimmune diseases, often exhibit reduced vaccine efficacy. Studies have shown that patients with robust immune responses, such as those with a strong T-cell repertoire, tend to experience better clinical outcomes following vaccination, particularly when combined with checkpoint inhibitors like PD-1 or CTLA-4 blockers (Soltani et al., 2022). Patient characteristics such as gender and performance status (ECOG score) also influence vaccine efficacy. In a large clinical meta-analysis, male patients were found to have slightly better outcomes from ICIs combined with vaccines compared to females, particularly in melanoma trials. Additionally, patients with better performance status (ECOG 0) demonstrated improved overall survival and progression-free survival compared to those with poorer baseline health (Yang et al., 2019). 5.2 Vaccine type and dose optimization The type of cancer vaccine used, as well as the dose administered, can greatly affect its efficacy. Different vaccine types, including peptide vaccines, dendritic cell vaccines, and RNA/DNA vaccines, have shown varying degrees of success depending on the cancer type and patient profile. Peptide-based vaccines are often used for their ability to target specific tumor antigens, but their efficacy can be limited by the variability of immune responses among patients. On the other hand, dendritic cell vaccines, which stimulate a more robust immune response, have been effective in several cancers, including prostate and glioblastoma, when optimized for dose and delivery (Yan et al., 2020). Dose optimization is also essential for maximizing efficacy while minimizing adverse effects. In studies comparing low and high-dose vaccines, high doses tend to produce stronger immune responses, but at the risk of increased side effects. A mathematical model exploring the synergy between cancer vaccines and ICIs demonstrated that an optimized combination of both agents, at lower doses than when used individually, could achieve maximal tumor reduction with fewer toxicities (Lai and Friedman, 2017). Personalized dosing strategies are also being explored. For example, neoantigen vaccines, which are highly personalized based on tumor-specific mutations, have shown promise in producing stronger and more targeted immune responses. Ongoing studies suggest that these personalized vaccines, when combined with appropriate dosing schedules, could offer improved survival outcomes in cancers such as melanoma and lung cancer (Liao et al., 2021). 5.3 Combination therapies One of the most promising strategies for enhancing the efficacy of cancer vaccines is combination therapy, particularly with immune checkpoint inhibitors (ICIs) like PD-1 and CTLA-4 blockers. Cancer vaccines alone have shown limited success in inducing durable clinical responses due to the immunosuppressive tumor microenvironment. However, when combined with ICIs, which lift the immune system's "brakes," the vaccine's ability to activate and sustain a robust anti-tumor response is significantly enhanced (Zhao et al., 2019).
RkJQdWJsaXNoZXIy MjQ4ODYzNQ==