Assessing the Efficacy of a Tumor Nanovaccine and Artificial Antigen Presenting Cell-Based System as a Combination Therapy in a Mouse Model of Melanoma

Abstract

Tumor cell lysate (TCL)-based vaccines contain a large number of tumor-specific and related antigens, albeit at low levels, that require active transfer and presentation by antigen-presenting cells (APCs) in vivo, which stimulate a weak immune response. The artificial APC (aAPC) system presented herein is a cell-based therapeutic system that can significantly enhance the immune response compared to TCL-based vaccines. This study combines these two treatment strategies to assess their in vitro and in vivo effects. We successfully prepared TCL-poly(lactic-co-glycolic acid)-PEI (TPP) and demonstrated that it was phagocytosed by the APCs and enhanced the maturation of DCs in vitro. The use of TPP in combination with the aAPCs resulted in better antitumor effects compared to the individual therapies. The combination therapy induced a higher proportion of CD4+ T, CD8+ T, and TRP2180–188-specific CD8+ T cells in comparison with the individual therapies. Additionally, the combination therapy enhanced the in vitro proliferation activity; greater inhibited regulatory T cells; and promoted inflammatory cytokine secretion, while reduced the production of inhibitory cytokines. In conclusion, the combination therapy consisting of the TPP tumor nanovaccine and the aAPC system enabled a broader immune response and achieve better antitumor effects compared to treatment with the individual therapies.

The quest for nanoparticle-powered vaccines in cancer immunotherapy

“…Currently, the artificial APC (aAPC) technique stands as a cell-based therapeutic approach that can significantly enhance the immune response in comparison to TCL-based vaccinations [ 347 ]. NPs act as an effective carrier of antigen and promote the effective presentation of antigen to immune cells [ 348 ].…”

“…An investigation by Song revealed that the combination of TCL-poly (lactic-co-glycolic acid)-PEI (TPP) tumor nanovaccines and aAPCs induced a greater immune response and achieved better antitumor results than individual therapies. This combined therapy increased proliferation activities, inhibited regulatory T cells, promoted inflammatory cytokine production, and reduced inhibitory cytokine production [ 347 ]. Lipid NPs, due to their lipid bilayer structure, are well suited to simulate cell membranes and enhance antigen presentation and subsequent immune response [ 349 ].…”