Journal of Vaccine Research 2024, Vol.14, No.5, 255-268 http://medscipublisher.com/index.php/jvr 260 be safe and immunogenic in non-metastatic breast cancer patients, generating high levels of antigen-specific T-cells (Stanton et al., 2023). Overall, HER2-targeted vaccines represent a promising avenue for enhancing anti-tumor immunity in breast cancer patients, with ongoing research focused on optimizing vaccine formulations and delivery methods to improve clinical outcomes. 5.2 T-cell and antibody responses The efficacy of HER2-targeted vaccines largely depends on their ability to elicit robust T-cell and antibody responses. T-cells, particularly CD8+ cytotoxic T lymphocytes (CTLs), play a crucial role in directly killing cancer cells, while antibodies can mediate antibody-dependent cellular cytotoxicity (ADCC) and other immune mechanisms. Several studies have demonstrated the potential of HER2-targeted vaccines to induce strong T-cell responses. For instance, a Phase I/II trial showed that HER2-specific T-cells could be significantly augmented in patients receiving HER2 vaccine-primed T-cell infusions, with 82% of patients exhibiting enhanced T-cell responses to at least one immunizing epitope (Disis et al., 2023). Another study reported that a HER2 plasmid DNA vaccine induced significant MHC class II-restricted T-cell responses, which were detectable for several years after vaccination . In addition to T-cell responses, HER2-targeted vaccines can also stimulate the production of HER2-specific antibodies. A pilot clinical trial demonstrated that a HER2 plasmid DNA vaccine, administered with GM-CSF and IL-2, induced long-lasting HER2-specific antibodies in a subset of patients. Furthermore, combining HER2-targeted vaccines with monoclonal antibodies, such as trastuzumab, has been shown to enhance CD8+ T-cell effector function and improve tumor-free survival in preclinical models (Wolpoe et al., 2003). Overall, the ability of HER2-targeted vaccines to elicit both T-cell and antibody responses is critical for their therapeutic efficacy, with ongoing research aimed at optimizing vaccine formulations to maximize these immune responses. 5.3 Patient survival and immunity maintenance The long-term benefits of HER2-targeted vaccines in breast cancer patients are reflected in improved survival rates and sustained immune responses. Clinical trials have provided evidence that these vaccines can enhance overall survival and maintain immunity over extended periods. A Phase I/II trial reported that patients receiving HER2 vaccine-primed T-cell infusions had a median survival of 45.0 months for responders, compared to 20.5 months for those with progressive disease (Figure 2) (Disis et al., 2023). Another study demonstrated that HER2-specific T-cell immunity elicited by a HER2 peptide vaccine was durable, with 75% of evaluable patients maintaining T-cell responses to HER2 peptides more than a decade after vaccination. This long-term immunity was associated with improved overall survival, with patients who developed epitope spreading showing a median survival of 84 months compared to 25 months for those who did not (Salazar et al., 2016). The combination of HER2-targeted vaccines with other therapies, such as trastuzumab, has also shown promise in extending patient survival. A study evaluating concurrent trastuzumab and HER2/neu-specific vaccination reported prolonged, robust immune responses and a median overall survival that had not been reached at a median follow-up of 36 months. In conclusion, HER2-targeted vaccines have demonstrated the potential to improve survival and maintain long-term immunity in breast cancer patients. Continued research and clinical trials are essential to further elucidate the mechanisms underlying these benefits and to optimize vaccine strategies for broader clinical application.
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