Abstract
Ovarian cancer is the most lethal gynecological malignancy with high recurrence rates and low survival rates, remaining a disease of high unmet need. Cancer immunotherapy, which harnesses the potential of the immune system to attack tumors, has emerged as one of the most promising treatment options in recent years. As an important form of immunotherapy, dendritic cell (DC)–based vaccines have demonstrated the ability to induce an immune response, while clinical efficacy of DC vaccines remains unsubstantiated as long‐term benefit is only reported in a restricted proportion of patients. Here, a biomimetic nanovaccine derived from DCs is developed through cell membrane coating nanotechnology. This nanovaccine, denoted “mini DC,” inherits the ability of antigen presentation and T cells' stimulation from DCs and is shown to elicit enhanced activation of T cells both in vitro and in vivo. In a mouse model of ovarian cancer, mini DCs exhibit superior therapeutic and prophylactic efficacy against cancer including delayed tumor growth and reduced tumor metastasis compared with DC vaccine. These findings suggest that mini DCs may serve as a facile and potent vaccine to boost anticancer immunotherapy.
Highlights
Ovarian cancer is the most lethal gynecological malignancy with high recurcavity.[3,4] The current first-line treatment for ovarian cancer is debulking surgery rence rates and low survival rates, remaining a disease of high unmet need
Trypan blue staining showed that HOCl-oxidized tumor cells had a cell viability of 0%, and homogenization could effectively enhance the uptake of tumor cell lysate by bone marrow–derived dendritic cells (BMDCs) (Figure S1, Supporting Information)
As one of important cytokines involving in the expansion and differentiation of T cells, IL-2 was loaded into the poly(lactic-co-glycolic acid) (PLGA) nanoparticle (PLGA-NP) during the synthesis process
Summary
To fabricate mini DC, bone marrow–derived dendritic cells (BMDCs) were pulsed with homogenized ID8 murine ovarian tumor cell lysate after HOCl oxidation as reported in previous studies.[32,33] Trypan blue staining showed that HOCl-oxidized tumor cells had a cell viability of 0%, and homogenization could effectively enhance the uptake of tumor cell lysate by BMDC (Figure S1, Supporting Information). Transmission electron microscopy (TEM) imaging after uranyl acetate negative staining showed that PLGA-NP was fully encapsulated into DCs’ membrane and the resulting nanoparticles, mini DC, possessed a core–shell structure with a diameter of about 160–170 nm (Figure 2B; Figure S2, Supporting Information). Flow cytometry confirmed that significantly increased mean fluorescence intensity (MFI) was observed on cells incubated with mini DC, but not with PLGA-NP (Figure 3B,C). No significant difference of fluorescence was observed when mini DC and PLGA-NP were incubated with NIH-3T3 cells at the same condition (Figure 3D–F). These findings demonstrate the binding ability of mini DC to T cells conferred by their DCs’ membrane enclosing. The result of ELISA indicated that mini DC could strongly promote the secretion of proinflammatory cytokines interferon (IFN)-γ and tumor necrosis factor (TNF)-α from T cells, which are important markers of activated cytotoxic T cells (Figure 3K,L).[39]
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