International Journal of Clinical Case Reports 2024, Vol.14, No.5, 230-241 http://medscipublisher.com/index.php/ijccr 232 overall survival (OS). In the case of glioblastoma, a Phase II trial of the dendritic cell vaccine Audencel showed no significant improvement in OS or PFS, despite generating immune responses. This highlighted the challenge of translating immunogenicity into clinical efficacy, particularly in aggressive cancers like glioblastoma (Buchroithner et al., 2018). Phase III trials are the most critical, comparing the vaccine's efficacy to the standard of care in large, randomized populations. These trials provide the strongest evidence of clinical benefit. For instance, sipuleucel-T's Phase III trials in prostate cancer established its ability to improve overall survival, leading to its approval. However, other vaccines, such as those for lung cancer, have shown mixed results in Phase III trials, with some improving survival but failing to significantly extend progression-free survival (Wang et al., 2015). 2.4 Efficacy evaluation: overall survival, progression-free survival, tumor response rate Evaluating the efficacy of cancer vaccines involves several key metrics, with overall survival (OS) being the gold standard. Many successful trials have demonstrated significant OS improvements without corresponding benefits in progression-free survival (PFS) or tumor response rates (TRR). For instance, studies on sipuleucel-T and prostvac-VF in prostate cancer showed that while PFS did not improve, OS increased, indicating the potential long-term benefits of immunotherapy beyond early disease progression (Dillman, 2015). Progression-free survival (PFS) is often used as a surrogate endpoint, measuring the time before disease progression. However, its validity as an indicator of overall survival is debated. In glioblastoma and lung cancer, some vaccines improved PFS but failed to demonstrate corresponding improvements in OS, suggesting that PFS alone may not fully capture the vaccine's long-term impact on patient outcomes (Lakdawalla et al., 2017). This disconnect highlights the complexity of evaluating vaccine efficacy, where immune modulation may have delayed but significant effects on survival. Tumor response rate (TRR), which measures the reduction in tumor size, is another important endpoint. However, in cancer vaccines, a high TRR does not always translate to improved survival. Some patients may experience stable disease with limited tumor shrinkage but still benefit from prolonged survival due to immune system engagement. In lung cancer, vaccines have shown modest TRR improvements, but their primary value lies in their ability to prolong survival while reducing side effects compared to conventional therapies (Wang et al., 2015). 3 Correlation Between Immune Response and Efficacy 3.1 Immunogenicity of cancer vaccines The immunogenicity of cancer vaccines refers to their ability to induce a measurable immune response, typically involving the activation of cytotoxic T lymphocytes (CTLs) that target and destroy cancer cells. Cancer vaccines are designed to elicit a response against tumor-associated antigens (TAAs) or neoantigens specific to the tumor. The effectiveness of this immune activation often depends on factors such as the nature of the antigen, the delivery method of the vaccine, and the immunological context of the patient. For instance, peptide vaccines targeting proteins like HER2/neu or MUC1 in breast cancer have shown promising results in eliciting robust CD8+ and CD4+ T cell responses, which are crucial for tumor control (Peres et al., 2015). However, the immunogenicity of cancer vaccines can be suboptimal in certain contexts. Tumors often create an immunosuppressive microenvironment that inhibits the immune system's ability to recognize and destroy cancer cells. Mechanisms such as upregulation of immune checkpoints (e.g., PD-1, CTLA-4) or recruitment of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) can blunt the immune response triggered by vaccines. Despite advances in vaccine design, many vaccines fail to generate a sufficiently strong or sustained immune response to control tumor progression on their own, leading researchers to explore combination therapies to enhance immunogenicity (Pilla et al., 2018). Recent studies have focused on improving vaccine immunogenicity through various strategies, such as the use of adjuvants, optimized delivery platforms, and neoantigen vaccines. Neoantigen vaccines, which are highly specific to individual tumors, have shown great potential in increasing immunogenicity by targeting mutations unique to
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