Immunization with mannosylated nanovaccines and inhibition of the immune-suppressing microenvironment sensitizes melanoma to immune checkpoint modulators

Abstract

Ibrutinib sensitizes melanoma to immune checkpoint modulators following immunization with nano-vaccines by relieving immune-suppressing microenvironment One Sentence Summary: Combination of dendritic cell-targeted nano-vaccines with a myeloid-derived suppressor cell inhibitor and immune checkpoint modulators expands the host antitumor immune cells, restricts tumour growth and prolongs survival in an orthotopic melanoma model.

Nanosystems for Improved Targeted Therapies in Melanoma

“…Conniot J. et al (2019) from Tel Aviv University showed that nanoparticles could potentially be used in the treatment of melanoma, similar to the use of vaccines for viral diseases [42]. The researchers ingeniously combined passive and active immunotherapy.…”

“…The nanoparticles, made of biodegradable polymer and sized at 160-190 nanometers, were individually packed with two peptides expressed in melanoma cells: Melan-A/MART-1(26-35(A27L)) major histocompatibility complex class I (MHCI)-restricted peptide (MHCI-ag) and the Melan-A/MART-1(51-73) MHCII-restricted peptide (MHCII-ag), directed towards the MHC class I and class II antigen presentation pathways [42]. They grafted the nanoparticles with mannose receptors, making them capable of ligand-mediated (active) targeting of dendritic cells [42]. The mannosylated nanovaccines were combined with an anti-PD-1 antibody (αPD-1) for immunosuppression blockade and an anti-OX40 antibody (αOX40) for T cell stimulation [42].…”

“…They grafted the nanoparticles with mannose receptors, making them capable of ligand-mediated (active) targeting of dendritic cells [42]. The mannosylated nanovaccines were combined with an anti-PD-1 antibody (αPD-1) for immunosuppression blockade and an anti-OX40 antibody (αOX40) for T cell stimulation [42]. After injecting the nanovaccines into mice models, they examined their effectiveness and found that it had both a prophylactic effect, preventing the development of melanoma in healthy immunized mice, and a therapeutic effect, significantly delaying the progression of the disease even in late-stage melanoma mice [42].…”

Tumor Cell Membrane‐Coated Liquid Metal Nanovaccine for Tumor Preventionǂ

“…Most of the current strategies deliver antigens to APCs in lymph node through a passive drainage effect, which can be inefficient or otherwise cause immune tolerance. Some studies have utilized a glycosylation strategy to enhance the affinity of nanovaccines with APCs, but it suffered from low immune cells density within vaccination site . These problems raise the question whether we can develop a strategy that would actively induce immune cells recruitment, enhance antigens uptake and activation in situ .…”

“Tuning aggregativeversusnon-aggregative lectin binding with glycosylated nanoparticles by the nature of the polymer ligand”

“…For example, sialic acid polymers have been used as decoys for the influenza hemagglutinins enabling nM affinity, 6,7 galactosylated polymers as inhibitors of the cholera toxin 8,9 and dendrimers to target galectins 10 and has been extensively reviewed. [11][12][13] Glycomaterials are emerging as tools to modulate complex cellular function: Godula and co-workers remodelled neural progenitor cells with sulphated glycans to control their differentiation, 14 mannosylated nanoparticles can potentiate vaccines 15 and glycosylated nanomaterials have been used to aid cellular delivery. [16][17][18][19][20] For instance, glucose-and galactosecoated iron oxide nanoparticles have been prepared and the influence of the glycan versus poly(ethylene glycol)-coating on the cellular uptake by several cell lines has been studied.…”