A facile approach to enhance antigen response for personalized cancer vaccination

Abstract

Existing strategies to enhance peptide immunogenicity for cancer vaccination generally require direct peptide alteration, which beyond practical issues may impact peptide presentation and result in vaccine variability. Here, we report a simple adsorption approach using polyethyleneimine (PEI) in a mesoporous silica micro-rod (MSR) vaccine to enhance antigen immunogenicity. The MSR-PEI vaccine significantly enhanced host dendritic cell activation and T cell response over the existing MSR vaccine and bolus vaccine formulations. Impressively, a single injection of the MSR-PEI vaccine using an E7 peptide completely eradicated large established TC-1 tumors in ~80% of mice and generated immunological memory. When immunized with a pool of B16F10 or CT26 neoantigens, the MSR-PEI vaccine eradicated established lung metastases, controlled tumor growth and synergized with anti-CTLA4 therapy. Our findings using three independent tumor models suggest that the MSR-PEI vaccine approach may serve as a facile and powerful multi-antigen platform to enable robust personalized cancer vaccination.

Materials for Immunotherapy

“…Both groups discovered that surface modification plays a major role in altering the inherent inflammatory response, leukocyte infiltration profile, and ultimately vaccine potency. In one study in 2018, the Mooney group adsorbed PEI to the surfaces of mesoporous silica microrods to enhance antigen immunogenicity via increased dendritic cell activation and CTL responses . In a second study in 2018, Mooney and co‐workers coated mesoporous silica rod scaffolds with lipid bilayers to mimic the endogenous ability of APCs to permit the fluid movement of antigens and costimulatory molecules within the membrane surface .…”

Expandable Immunotherapeutic Nanoplatforms Engineered from Cytomembranes of Hybrid Cells Derived from Cancer and Dendritic Cells

“…CD86 is a protein expressed on DCs that provides costimulatory signal necessary for T cell activation and survival, and the expression level of CD86 increases in the meantime when DCs are mature . TNF‐α, an important marker in the activation of cellular immunity, could regulate immune cells . To understand better the in vivo antitumor immune mechanism in distant tumors, the immunohistochemistry of CD86 and immunofluorescence of TNF‐α assays of distant tumors were conducted to research the mature of DCs and secretion of immune factor.…”

Single-shot Mesoporous Silica Rods Scaffold for Induction of Humoral Responses Against Small Antigens

“…10-12 weeks later, mice were euthanized and their draining lymph nodes, spleen and a lower limb harvested. Lymph nodes and spleens were processed in to single cells suspensions as described previously [52] .…”

“…Using this approach, an implantable poly(lactideco-glycolide) (PLGA) based scaffold cancer vaccine was shown to induce complete melanoma regression in subsets of mice [27] . To eliminate the need for surgical implantation, we recently developed a new approach of injectable scaffolds using mesoporous silica rods (MSR) microparticles [28,29] . We demonstrated that MSR microparticles could spontaneously assemble into a 3D scaffold after subcutaneous injection; the macropores formed by random particle stacking allowed for cell infiltration and active cell-scaffold interactions.…”