Journal of Vaccine Research 2024, Vol.14, No.5, 255-268 http://medscipublisher.com/index.php/jvr 258 responses. For example, a dual-epitope DC vaccine targeting two different HER2 peptides has been shown to generate significant T cell responses and clinical benefits in patients with HER2-overexpressing breast cancer (Vincent et al., 2023). This approach has been associated with stable disease and partial responses in a subset of patients, indicating its potential for clinical application. Moreover, targeting multiple antigens can also help in overcoming the limitations of single-antigen vaccines, such as antigen loss or mutation. By presenting a broader array of antigens, multi-antigen vaccines can enhance the likelihood of effective tumor recognition and destruction by the immune system. This strategy holds promise for improving the efficacy of cancer vaccines and providing durable clinical benefits for breast cancer patients. In conclusion, the clinical applications of cancer vaccines in breast cancer are diverse and evolving. HER2/neu-based vaccines, dendritic cell vaccines, and multi-antigen vaccines each offer unique advantages and have shown promising results in preclinical and clinical studies. Continued research and optimization of these vaccine strategies are essential for realizing their full potential in the treatment of breast cancer. 4 Long-Term Immunological Effects of Cancer Vaccines Cancer vaccines have emerged as a promising strategy in the fight against breast cancer, particularly in enhancing the immune system's ability to recognize and destroy cancer cells. The long-term immunological effects of these vaccines are crucial for understanding their potential in providing sustained protection and preventing recurrence. This study delves into the persistence of T-cell responses, antibody-mediated immunity, and the role of these vaccines in recurrence prevention. 4.1 Persistence of T-cell responses The persistence of T-cell responses is a critical factor in the long-term efficacy of cancer vaccines. Studies have shown that cancer vaccines can induce robust and durable T-cell responses in breast cancer patients. For instance, a study on a HER2/neu vaccine demonstrated that patients who were immunized showed persistent T-cell immunity years after the initial vaccination. Specifically, 75% of evaluable patients had long-term T-cell immunity to HER2 peptides, and 88% exhibited epitope spreading, which is the ability of the immune system to recognize and respond to multiple epitopes of the HER2 protein (Salazar et al., 2016). This long-term T-cell response is associated with improved overall survival, highlighting the potential of cancer vaccines to provide lasting immunological benefits. Another study on personalized peptide vaccination (PPV) in breast cancer patients without active tumors at the time of vaccination found that while cytotoxic T lymphocyte (CTL) levels were initially boosted, they declined over time, indicating a transient nature of cellular immunity. However, the initial boost in CTL activity was significant, suggesting that periodic booster vaccinations might be necessary to maintain long-term T-cell responses (Suekane et al., 2022). These findings underscore the importance of understanding the dynamics of T-cell persistence and the potential need for booster doses to sustain immunity. 4.2 Antibody-mediated immunity Antibody-mediated immunity plays a vital role in the long-term protection offered by cancer vaccines. The generation of specific antibodies against tumor-associated antigens can help in the continuous surveillance and elimination of cancer cells. In a phase I trial of a plasmid DNA vaccine encoding the ERBB2 intracellular domain, patients exhibited robust and long-lasting antibody responses against ERBB2. The study found that higher vaccine doses were associated with stronger antibody responses, which were maintained over time (Disis et al., 2022). This suggests that optimizing vaccine dosage is crucial for achieving sustained antibody-mediated immunity (Figure 1). Similarly, a study on a multi-epitope HER2 vaccine combined with trastuzumab showed that the vaccine generated long-lasting T-cell and antibody responses in patients with HER2-positive breast cancer. The combination of the vaccine with trastuzumab not only enhanced the immune response but also contributed to better clinical outcomes (Chumsri et al., 2022). These findings highlight the potential of cancer vaccines to induce durable antibody responses, which are essential for long-term cancer control.
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