Host: The Japanese Society of Toxicology
We have developed a new Toll-like receptor 3-specific adjuvant, named ARNAX, which specifically stimulates dendritic cells (DCs), and enables us to prime DCs safely without inflammation. Thus, administration of ARNAX with antigens in hosts guarantees antigen-specific CTL proliferation without cytokine toxicity. ARNAX consists of GpC DNA-cap and 120mer dsRNA, and targets TLR3 in DCs. We have established the strategy for a large-scale synthesis of ARNAX and defined its function for DC-priming without inflammation. Thus, immune-enhancing occurs independent of inflammation in hosts.
In mouse tumor-implant models, immunotherapy with ARNAX and exogenous tumor antigen efficiently induces regression of various implant tumors and prolonged survival time. Even without identification of tumor antigen, combination therapy with ARNAX and PD-1/L1 Ab additively induces proliferation of tumor-specific CTLs and their infiltration into tumor tissues, leading to enhanced tumor regression and prolonged survival. Non-inflammatory tumor vaccine would be feasible using ARNAX.
Adjuvants usually harbor cytokine toxicity, which is a great barrier against vaccine approval. There are a number of prophylactic vaccines against viral infectious diseases. Here we offer an ideal recipe of harmless adjuvant for vaccines against infectious diseases as well as cancers. We are obtaining non-clinical POC on ARNAX plus antigen in prophylactic vaccines against viral infections. We are planning toxicity and safety tests to make a protocol for the clinical test for POC in patients with cancer.
