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.
Department of Clinical Oncology, Tohoku University Hospital, Sendai 980-8577, Japan. Shirota@idac.tohoku.ac.jp.
Hidekazu
H
Shirota
Cancer and Inflammation Program, National Cancer Institute, Frederick, MD 21702, USA. Trossd@mail.nih.gov.
Debra
D
Tross
Cancer and Inflammation Program, National Cancer Institute, Frederick, MD 21702, USA. klinmand@mail.nih.gov.
Dennis M
DM
Klinman
CpG; TLR; cancer; vaccine