Self-healing microcapsules synergetically modulate immunization microenvironments for potent cancer vaccination

Abstract

Therapeutic cancer vaccines that harness the immune system to reject cancer cells have shown great promise for cancer treatment. Although a wave of efforts have spurred to improve the therapeutic effect, unfavorable immunization microenvironment along with a complicated preparation process and frequent vaccinations substantially compromise the performance. Here, we report a novel microcapsule-based formulation for high-performance cancer vaccinations. The special self-healing feature provides a mild and efficient paradigm for antigen microencapsulation. After vaccination, these microcapsules create a favorable immunization microenvironment in situ, wherein antigen release kinetics, recruited cell behavior, and acid surrounding work in a synergetic manner. In this case, we can effectively increase the antigen utilization, improve the antigen presentation, and activate antigen presenting cells. As a result, effective T cell response, potent tumor inhibition, antimetastatic effects, and prevention of postsurgical recurrence are achieved with various types of antigens, while neoantigen was encapsuled and evaluated in different tumor models.

Visualizable Delivery of Nanodisc Antigen-Conjugated Adjuvant for Cancer Immunotherapy

“…Apart from CCR7, the dynamics of the cytoskeleton is another indispensable indicator for DCs motility. 36 As the two major components of cytoskeleton, microfilaments and microtubules were then analyzed via immunofluorescence assays. The results given in Figure S4C reveal that the DCs incubated with Cy-OVA@CpG nanovaccines exhibit a typical motility phenotype showing strong signals from filamentous actin and extended veils, contrasting to those in the control groups showing weak filament based phenotype.…”

Harnessing Innate Immunity Using Biomaterials for Cancer Immunotherapy

“…[ 40 ] In one example, mesoporous MPs constructed with PEG‐poly‐ dl ‐lactide were employed to load MPLA and antigens, inducing long‐lasting antitumor immunity. [ 41 ] The MPs were designed to be slowly degraded at tumor extracellular pH. [ 41 ] This delivery method allowed for sustained release of the MPLA and antigen as well as stimulation of APCs without the previous toxicities of MPLA alone, thereby driving specific CTL responses over long periods to eradicate the inoculated tumor and its metastasis with an outstanding safety profile.…”

“…[ 41 ] This delivery method allowed for sustained release of the MPLA and antigen as well as stimulation of APCs without the previous toxicities of MPLA alone, thereby driving specific CTL responses over long periods to eradicate the inoculated tumor and its metastasis with an outstanding safety profile. [ 41 ] As another type of TLR4 agonist, human papillomavirus (HPV) has been shown to induced tumor‐specific CTL responses in several types of cancer in Phase I/II clinical trials. [ 42 ] As with MPLA, nonspecific targeting of HPV is likely to cause cytokine storm, again benefitting from formulations with biomaterials.…”

Nanomaterial-based delivery vehicles for therapeutic cancer vaccine development

“…Ma et al 126 engineered several homogeneous chitosan, PLGA, and PLA-based chassis particles, which displayed antigens on macro/nanoparticles, and which supported excellent antigen delivery and functioned as superior immunostimulants 127 . To further improve immune recognition, Xia et al 128 constructed a deformable engineered vaccine using PLGA nanoparticles instead of surfactants, where antigens were assembled on a dynamic flexible emulsion chassis to increase the preventive and therapeutic effects.…”