Recruiting T‐Cells toward the Brain for Enhanced Glioblastoma Immunotherapeutic Efficacy by Co‐Delivery of Cytokines and Immune Checkpoint Antibodies with Macrophage‐Membrane‐Camouflaged Nanovesicles

Abstract

Immunotherapy with immune checkpoint inhibitors (CPIs) shows promising prospects for glioblastoma multiforme (GBM) but with restricted results, mainly attributed to the immunosuppressive tumor microenvironment (TME) and the limited antibody permeability of the blood-tumor barrier (BTB) in GBM. Here, nanovesicles with a macrophage-mimicking membrane are described, that co-deliver chemotactic CXC chemokine ligand 10 (CXCL10), to pre-activate the immune microenvironment, and anti-programmed death ligand 1 antibody (aPD-L1), to interrupt the immune checkpoint, aiming to enhance the effect of GBM immunotherapy. Consequently, the tumor tropism of the macrophage membrane and the receptor-mediated transcytosis of the angiopep-2 peptide allow the nanovesicle to effectively cross the BTB and target the GBM region, with 19.75-fold higher accumulation of antibodies compared to the free aPD-L1 group. The CPI therapeutic efficacy is greatly enhanced by CXCL10-induced T-cells recruitment with significant expansion of CD8 + T-cells and effector memory T-cells, leading to the elimination of tumor, prolonged survival time, and long-term immune memory in orthotopic GBM mice. The nanovesicles, that relieve the tumor immunosuppressive microenvironment by CXCL10 to enhance aPD-L1 efficacy, may present a promising strategy for brain-tumor immunotherapy.

Recent advances in nanotechnology for programmed death ligand 1-targeted cancer theranostics

“…7(d)). 71 A2 is a peptide that targets the low-density lipoprotein receptor-related protein 1 (LRP-1), also known as Angiopep-2 peptide. The nanocarrier with excellent GBM specificity and BTB penetrability can be ascribed to the tumor tropism of the macrophage membrane and the targeting ability of BTB-shuttle peptide.…”

Multifaceted Carbonized Metal–Organic Frameworks Synergize with Immune Checkpoint Inhibitors for Precision and Augmented Cuproptosis Cancer Therapy

“…These findings indicate that ICIs can serve as an adjunctive therapy for cancer, effectively reactivating the body’s innate immune response against tumors. , Notably, by impeding the evasion tactics employed by tumor cells, ICIs can not only enhance the immune system’s ability to detect and eradicate tumor cells but also stimulate long-term immune memory, thereby aiding in the prevention of tumor metastasis and recurrence. This approach tackles the constraints associated with cancer therapies that are solely based on apoptosis, which is insufficient for complete tumor eradication, and addresses the challenges of tumor metastasis and recurrence. , …”

“…This approach tackles the constraints associated with cancer therapies that are solely based on apoptosis, which is insufficient for complete tumor eradication, and addresses the challenges of tumor metastasis and recurrence. 29,30 Metal−organic frameworks (MOFs) have garnered significant attention in recent years owing to their structural versatility, tunable properties, and diverse range of applications. 31−34 In particular, MOF derivatives (modified versions of MOFs) have shown potential in drug delivery, diagnostic imaging, and photodynamic therapy for cancer, among other modalities.…”