Nanovesicle‐Mediated Targeted Delivery of Immune Checkpoint Blockades to Potentiate Therapeutic Efficacy and Prevent Side Effects

Abstract

Despite the clinically proven efficacies of immune checkpoint blockades, including anti‐cytotoxic T lymphocyte‐associated protein 4 antibody (αCTLA‐4), the low response rate and immune‐related adverse events (irAEs) in cancer patients represent major drawbacks of the therapy. These drawbacks of αCTLA‐4 therapy are mainly due to the suboptimal activation of tumor‐specific cytotoxic T lymphocytes (CTLs) and the systemic nonspecific activation of T cells. To overcome such drawbacks, αCTLA‐4 is delivered by dendritic cell‐derived nanovesicles presenting tumor antigens (DCNV‐TAs) that exclusively interact with tumor‐specific T cells, leading to selective activation of tumor‐specific CTLs. Compared to conventional αCTLA‐4 therapy, treatment with αCTLA‐4‐conjugated DCNV‐TAs significantly inhibits tumor growth and reduces irAEs in syngeneic tumor‐bearing mice. This study demonstrates that the spatiotemporal presentation of both αCTLA‐4 and tumor antigens enables selective activation of tumor‐specific T cells and potentiates the antitumor efficacy of αCTLA‐4 without inducing systemic irAEs.

Boosting Checkpoint Immunotherapy with Biomaterials

“…Jung et al developed a biomimetic nanovesicle (αCTLA-4@DCNV-TA) by conjugating αCTLA-4 and tumor antigen to the serial extruded mature DC membrane nanovesicle (DCNV) (Figure 15F). 263 Compared to conventional αCTLA-4 injection therapy, administration with αCTLA-4@DCNV-TAs significantly generated effective tumor-specific CTLs (Figure 15G) to control tumor growth and, most importantly, decrease irAEs in the syngeneic tumor model.…”

“…(G) Immunomodulation properties of αCTLA-4@DCNV-TA. (F,G) Reproduced with permission from ref . Copyright 2022 Wiley.…”

Tumor–Antigen Activated Dendritic Cell Membrane-Coated Biomimetic Nanoparticles with Orchestrating Immune Responses Promote Therapeutic Efficacy against Glioma

“…T cell dysfunction caused by persistent antigen stimulation triggers exhaustion. Tim-3 expression and PD-1 expression of T cells have been identified as markers of T cell exhaustion . As a large secondary lymphoid organ, the spleen is the primary site for T cell activation.…”

“…Tim-3 expression and PD-1 expression of T cells have been identified as markers of T cell exhaustion. 39 As a large secondary lymphoid organ, the spleen is the primary site for T cell activation. We explored the frequency of exhausted T cells in the spleen and found that the aDCM@ PLGA/RAPA group was a significant decrease in the frequency of PD-1 + TIM3 + CD8 + T cells compared with other groups (Figure 4H,I), indicating that tumor-infiltrating T cells can exert more antitumor effects.…”

Iron Oxide Nanoparticle-Incorporated Mesenchymal Stem Cells for Alzheimer’s Disease Treatment

“…It is well-known that MSCs promote the proliferation and angiogenesis of endothelial cells, exert anti-inflammatory effects by polarizing microglia from pro-inflammatory M1 microglia to anti-inflammatory M2 microglia, and stimulate astrocytes to express neurotrophic, antiapoptotic, and angiogenic factors. , First, we evaluated the angiogenic efficacy of MSC-IONPs by a capillary tube formation assay using cocultures of human umbilical vein endothelial cells (HUVECs) and MSCs in a trans-well system. In the IONP-treated groups, an amount equal to the amount of IONPs contained in the MSC-IONPs was added.…”