Targeted Cancer Immunotherapy: Nanoformulation Engineering and Clinical Translation.

With the rapid growth of advanced nanoengineering strategies, there are great implications for therapeutic immunostimulators formulated in nanomaterials to combat cancer. It is crucial to direct immunostimulators to the right tissue and specific immune cells at the right time, thereby orchestrating the desired, potent, and durable immune response against cancer. The flexibility of nanoformulations in size, topology, softness, and multifunctionality allows precise regulation of nano-immunological activities for enhanced therapeutic effect. To grasp the modulation of immune response, research efforts are needed to understand the interactions of immune cells at lymph organs and tumor tissues, where the nanoformulations guide the immunostimulators to function on tissue specific subsets of immune cells. In this review, recent advanced nanoformulations targeting specific subset of immune cells, such as dendritic cells (DCs), T cells, monocytes, macrophages, and natural killer (NK) cells are summarized and discussed, and clinical development of nano-paradigms for targeted cancer immunotherapy is highlighted. Here the focus is on the targeting nanoformulations that can passively or actively target certain immune cells by overcoming the physiobiological barriers, instead of directly injecting into tissues. The opportunities and remaining obstacles for the clinical translation of immune cell targeting nanoformulations in cancer therapy are also discussed.