A personalized vaccine combining immunogenic cell death-induced cells and nanosized antigens for enhanced antitumor...

The tumor vaccine aims to activate the immune system, promote antitumor cellular responses, and restore immune recognition and clearance of tumor cells. However, the low immunogenicity and heterogeneity of tumor antigens, along with immunosuppressive mechanisms, severely hinder tumor vaccines from achieving an efficient and sustained antitumor effect. Herein, we developed a combined vaccine strategy that utilizes immunogenic cell death (ICD) to elicit a broad spectrum of antigen-specific responses in a whole-cell-based manner. Additionally, we introduced nanosized antigens to intensify immune responses targeting a key tumor antigen. The combination of mitoxantrone (MTX) and curcumin (Cur) optimized ICD properties in TC-1 tumor cells, as evidenced by increased release of "find me" signals, such as HMGB1 and ATP, and enhanced exposure of the "eat me" signal, CALR, compared to either MTX or Cur alone. Correspondingly, the ICD cells induced by the combination produced more significant antitumor effects in vivo. Furthermore, the ICD cells in combination with E7-HBcAg VLPs or E7-Q11 nanofibers induced more intense effector cell responses to the antigen included in the nanovaccines, as well as a broad spectrum of antigens provided by tumor cells, and significantly suppressed the growth of established tumors compared with either ICD cells, VLPs, or nanofibers alone. In conclusion, the combination of ICD cells and nanosized antigens produced synergistic antitumor effects and elicited robust and comprehensive antitumor immunity, presenting an attractive strategy for developing personalized tumor vaccines.