CpG Oligonucleotides as Cancer Vaccine Adjuvants
Adjuvants improve host responsiveness to co delivered vaccines through a variety of mechanisms. Agents that trigger cells expressing Toll like receptors (TLR) activate an innate immune response that enhances the induction of vaccine specific immunity. When administered in combination with vaccines designed to prevent or slow tumor growth, TLR agonists have significantly improved the generation of cytotoxic T lymphocytes. Unfortunately, vaccines containing TLR agonists have rarely been able to eliminate large established tumors when administered systemically. To improve efficacy, attention has focused on delivering TLR agonists intra tumorally with the intent of altering the tumor microenvironment. Agonists targeting TLRs 7/8 or 9 can reduce the frequency of Tregs while causing immunosuppressive MDSC in the tumor bed to differentiate into tumoricidal macrophages thereby enhancing tumor elimination. This work reviews pre clinical and clinical studies concerning the utility of TLR 7/8/9 agonists as adjuvants for tumor vaccines.
Vaccines