Journal of Vaccine Research 2024, Vol.14, No.4, 183-195 http://medscipublisher.com/index.php/jvr 187 3.5 Combination adjuvants Combination adjuvants involve the use of multiple adjuvant types to leverage their complementary mechanisms of action. For instance, combining TLR agonists with alum or oil-in-water emulsions can enhance both humoral and cellular immune responses, thereby improving the overall efficacy of cancer vaccines (Del Giudice et al., 2018; Cuzzubbo et al., 2021; Melssen et al., 2021). Studies have shown that such combinations can lead to more durable and potent immune responses, which are essential for effective cancer immunotherapy (Melssen et al., 2021; Heo et al., 2023). 3.6 Emerging adjuvants Emerging adjuvants are being developed to address the limitations of existing adjuvants and to enhance the efficacy of cancer vaccines further. These include novel TLR agonists, carbomer-based adjuvants, and other innovative formulations that aim to elicit balanced antibody and T-cell responses (Luchner et al., 2021; Lee and Suresh, 2022; Yang et al., 2022). The ongoing research and development in this area hold promise for the future of cancer vaccine adjuvants, potentially leading to more effective and personalized cancer immunotherapies (Yang et al., 2022). In summary, the use of adjuvants in cancer vaccines is crucial for enhancing their efficacy. Different types of adjuvants, including alum-based, oil-in-water emulsions, TLR agonists, saponin-based, combination adjuvants, and emerging adjuvants, each offer unique benefits and mechanisms of action that can be leveraged to improve cancer immunotherapy outcomes. 4 Preclinical and Clinical Studies on Adjuvants in Cancer Vaccines 4.1 Preclinical models Preclinical models have been instrumental in understanding the potential of various adjuvants in enhancing the efficacy of cancer vaccines. These models allow for the exploration of the mechanisms by which adjuvants can boost immune responses and provide insights into their safety and effectiveness before clinical trials. One notable example is the use of polyinosinic:polycytidylic acid (poly(I:C)) and its derivative poly-ICLC. These synthetic immunological danger signals have shown promise in preclinical studies by enhancing vaccine-induced anti-tumor immune responses and contributing to tumor elimination in animal models (Ammi et al., 2015). Similarly, nanoadjuvants have demonstrated unique advantages in preclinical settings. These novel adjuvants can enhance the magnitude, breadth, and durability of immune responses by influencing various factors such as size, surface charge, and morphology (Tan et al., 2022). Another innovative approach involves the use of multifunctional protein conjugates with built-in adjuvants. These constructs, which combine adjuvants and tumor-associated antigens in a single molecule, have shown significant potential in preclinical models. For instance, a three-in-one protein conjugate incorporating a TLR7 agonist and the tumor-associated antigen MUC1 significantly increased immune responses compared to traditional adjuvants (Du et al., 2020). 4.2 Clinical trials Despite the promising results in preclinical models, translating these findings into clinical success has been challenging. Many cancer vaccines have shown limited clinical efficacy, partly due to the use of less potent adjuvants in human trials compared to those used in animal studies (Khong and Overwijk, 2016). However, some adjuvants have shown promise in clinical settings. Poly-ICLC, for example, is currently being extensively studied in ongoing clinical trials. Early results suggest that it could become a part of future approved cancer immunotherapies due to its ability to enhance vaccine-induced anti-tumor immune responses (Ammi et al., 2015). Another promising adjuvant is IL-7, which plays a critical role in the development, maintenance, and proliferation of T lymphocytes. Clinical trials have shown that IL-7 can enhance T cell responses and memory, making it a potential adjuvant for cancer vaccines (Figure 3) (Zhao et al., 2022).
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