Albumin-binding toll-like receptor 7 agonist nanocomplexes elicit antitumor immunity for cancer immunotherapy

Toll-like receptor agonists have been extensively applied as immunostimulatory adjuvants because of their well-defined pharmacological mechanisms, while systemic administration of Toll-like receptor agonists have shown limited efficacy due to their unfavorable pharmacokinetic properties. Here we constructed an albumin-binding Toll-like receptor 7 agonist (Ab1V209) by conjugating the Toll-like receptor 7 agonist 1V209 with truncated Evans Blue for binding to endogenous albumin. The resulting Ab1V209 has the ability to hijack albumin and is retained in tumor tissues   for a higher accumulation than 1V209. As monotherapy, the systemic administration of Ab1V209 alters the function of tumor-associated macrophages towards anti-tumor phenotype, and increases the infiltration of CD8 + T cells, leading to controlled tumor growth with minimal systemic toxicity. When used in combination with an mRNA cancer vaccine, the combination therapy activated dendritic cells to provide antigen presentation molecule and co-stimulatory molecule, resulting in a strong T cell activation and expansion. This study presents a strategy for the rational engineering of albumin-binding adjuvants to enhance cancer immunotherapy.