Toll-like receptor agonists: current status and future perspective on their utility as adjuvants in improving anticancer vaccination strategies

Toll-like receptor (TLR) agonists possess remarkable properties, particularly with regard to dendritic cell activation, promoting Th1-type cytokine production and optimizing cytotoxic T-cell responses. Preclinical and clinical studies conducted to date show that TLR agonists can improve currently applied anticancer vaccination protocols. Although these have resulted in the US FDA approval of three TLR agonists for use in humans, their abundant application encounters limitations, principally due to dose-limiting toxicity evoking from systemic cytokine production. Here, using selected examples of clinical studies, we provide a concise review regarding the knowledge acquired thus far on the adjuvant use of TLR agonists as cancer vaccine components. We also provide evidence on the exploitation of a novel TLR agonist, prothymosin-alpha, which enhances the efficacy of tumor-reactive effectors without causing severe adverse effects.