Journal of Vaccine Research 2024, Vol.14, No.5, 255-268 http://medscipublisher.com/index.php/jvr 257 3 Clinical Applications of Cancer Vaccines in Breast Cancer Cancer vaccines represent a promising therapeutic approach in the treatment of breast cancer by stimulating the immune system to target and destroy cancer cells. These vaccines can be designed to target specific antigens expressed by breast cancer cells, thereby enhancing the body's immune response against the tumor. The clinical applications of cancer vaccines in breast cancer are diverse and include HER2/neu-based vaccines, dendritic cell vaccines, and multi-antigen vaccines. Each of these approaches has shown varying degrees of efficacy in preclinical and clinical studies, offering hope for improved treatment outcomes for breast cancer patients. 3.1 HER2/neu-based vaccines HER2/neu-based vaccines target the HER2/neu protein, which is overexpressed in a significant subset of breast cancers. These vaccines aim to elicit a robust immune response against HER2/neu-expressing tumor cells. One of the most clinically advanced HER2/neu-based vaccines is the E75 peptide vaccine, which has shown promise in both preclinical and clinical settings. The E75 peptide, derived from the HER2/neu protein, has been demonstrated to induce specific CD8+ T cell responses that can target and kill HER2/neu-expressing tumor cells (Tran et al., 2015). Recent studies have focused on optimizing the delivery of the E75 vaccine to enhance its efficacy. For instance, coupling the E75 peptide to the B-subunit of Shiga toxin (STxB) has been shown to improve the induction of multifunctional and high-avidity E75-specific CD8+ T cells, resulting in potent tumor protection in preclinical models. Additionally, combining the E75 vaccine with anti-HER2 monoclonal antibodies (mAbs) such as trastuzumab has been found to synergize in promoting tumor regression, particularly in tumors with low HER2/neu expression (Tran et al., 2015). These findings suggest that HER2/neu-based vaccines, especially when used in combination with other therapies, hold significant potential for improving outcomes in breast cancer patients. 3.2 Dendritic cell vaccines Dendritic cell (DC) vaccines represent another promising approach in the immunotherapy of breast cancer. DCs are potent antigen-presenting cells that can be engineered to present tumor antigens, thereby stimulating a robust immune response. HER2/neu-loaded DC vaccines have shown efficacy in preclinical models, where they have been demonstrated to induce strong CD4+and CD8+T cell responses, as well as humoral immunity against HER2/neu (Özverel et al., 2020). One innovative approach involves the intrathecal delivery of DC vaccines in models of leptomeningeal disease (LMD), a severe complication of breast cancer. Studies have shown that intrathecal administration of HER2/neu-pulsed DC vaccines can eradicate tumor growth and protect against disease re-inoculation in HER2+ and triple-negative breast cancer models. This method has been associated with prolonged survival and complete tumor regression in a significant proportion of treated mice, highlighting the potential of DC vaccines in managing advanced and metastatic breast cancer. Furthermore, combining DC vaccines with other immunotherapeutic agents, such as anti-PD-L1 mAbs and adjuvants like QS-21, has been shown to enhance their efficacy. This combination therapy has resulted in decreased tumor sizes, increased cytotoxic activity of splenocytes, and significant infiltration of immune cells into the tumor microenvironment (Özverel et al., 2020). These findings underscore the potential of DC vaccines as part of a multi-modal immunotherapy strategy for breast cancer. 3.3 Multi-antigen vaccines Multi-antigen vaccines aim to target multiple tumor-associated antigens simultaneously, thereby broadening the immune response and reducing the likelihood of immune escape. These vaccines can be designed to include a combination of peptides, proteins, or whole-cell lysates that represent various tumor antigens. The rationale behind multi-antigen vaccines is to induce a more comprehensive and robust immune response that can target different aspects of tumor biology. Preclinical studies have demonstrated the efficacy of multi-antigen vaccines in inducing potent antitumor immune
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