Lipid-based delivery of CpG oligodeoxynucleotides for cancer immunotherapy

Abstract

The anti-tumor activity of CpG-containing oligodeoxynucleotides (ODNs) has been well established in numerous animal models and confirmed in a number of early clinical trials. While the use of chemical modifications has effectively reduced the sensitivity of ODNs to nuclease degradation and a number of human trials have yielded promising results, the clinical utility of free CpG ODN still faces several significant challenges that must be addressed to achieve optimal potency and therapeutic activity. These include unfavorable pharmacokinetic/biodistribution characteristics, lack of specificity for target cells and poor intracellular uptake. To overcome these challenges, lipid-based delivery systems have been developed to protect the CpG ODN payload, modify their circulation/distribution characteristics, enhance immune cell targeting and facilitate intracellular uptake. In preclinical cancer models, lipid-mediated delivery has demonstrated the capacity to increase the immunopotency of CpG ODNs and dramatically enhance their anti-tumor efficacy as monotherapies, vaccine adjuvants and combination therapies with monoclonal antibodies or chemotherapy. This review will focus on investigating CpG ODNs as a cancer immunotherapeutic and the promising enhancement in efficacy that can be achieved through the use of lipid nanoparticles as delivery vehicles.