Personalized gel-droplet monocyte vaccines for cancer immunotherapy

Abstract

Among the numerous forms of cancer immunotherapy, cancer vaccines have attracted increasing attention because of their ability to elicit sustained antitumor immune responses and durable tumor regression. Here, a personalized gel-droplet monocyte vaccine (GEMA) derived from host blood was reported. A streamlined microfluidic vaccine production platform was designed to combine the separation of monocytes from host blood and the encapsulation of monocytes in an alginate gel droplet, which simplified the handling of the blood product and permitted the rapid preparation of vaccines. In addition, the application of alginate gel encapsulation not only improved the efficiency of antigen uptake by monocytes, but it also promoted the production of antigen-specific CD8⁺ T cells in the spleen, resulting in an intense cytotoxic T lymphocyte (CTL) response. Moreover, depending on the disease profile of a specific patient, different adjuvant- and antigen-loaded monocytes could be simultaneously encapsulated in gel droplets to prepare a cocktail vaccine based on patient needs. In this study, anti-PD-1 antibodies were encapsulated in gel droplets as a model adjuvant to obtain a cocktail vaccine, and this demonstrated enhanced antitumor efficacy in a 4T1 breast tumor model. In summary, this study provided a unique vaccine production strategy and an efficient combination therapy approach, holding great promise for the development of personalized cancer vaccines.