Hiroshi Shiku, Naozumi Harada and colleagues explain that most cancer vaccine candidates are designed to flag down immune cells, called macrophages and dendritic cells, that signal "killer" T cells to attack tumors. The problem is that approaches based on targeting these generally circulating immune cells have not been very successful. But recent research has suggested that a subset of macrophages only found deep inside lymph nodes could play a major role in slowing cancer. But how could one get a vaccine to these special immune cells without first being gobbled up by the macrophages and dendritic cells circulating in the body? Shiku's team wanted to see if stealthy nanoparticles they had developed and clinically tested in patients might hold the answer.
The researchers injected the nanoparticles into mice. They found that the particles, which have no electric charge or surface molecules that would attract the attention of circulating immune cells, were able to enter the mice's lymph nodes. But once inside the lymph nodes' core, the special kind of macrophage engulfed the particles. When molecules for signaling killer T cells were put inside the nanoparticles, they hindered tumor growth far better than existing vaccines.