Inducing Ectopic T Cell Clusters Using Stromal Vascular Fraction Spheroid-Based Immunotherapy to Enhance Anti-Tumor Immunity.

Tertiary lymphoid structures (TLSs) provide specialized niches for immune cells, resulting in improved prognoses for patients undergoing cancer immunotherapy. Shaping TLS-like niches may improve anti-cancer immunity and overcome the current limitations of immune cell-based immunotherapy. Here, it is shown that stromal vascular fraction (SVF) from adipose tissues can enhance dendritic cell (DC)-mediated T cell immunity by inducing ectopic T lymphocyte clusters. SVF cells expanded ex vivo have phenotypes and functions similar to those of fibroblastic reticular cells in a secondary lymphoid organ, and their properties can be modulated using three-dimensional spheroid culture and coculture with DCs spiked with antigen-loaded iron oxide-zinc oxide core-shell nanoparticles. Thereby, the combination of SVF spheroids and mature DCs significantly augments T cell recruitment and retention at the injection site. This strategy elicits enhanced antigen-specific immune response and anti-tumoral immunity in mice, illustrating the potential for a novel immunotherapeutic design using SVF as a structural scaffold for TLS.

Virus blocking textile for SARS-CoV-2 using human body triboelectric energy harvesting.

Effective mitigation technology to prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is required before achieving population immunity through vaccines. Here we demonstrate a virus-blocking textile (VBT) that repulses SARS-CoV-2 by applying repulsive Coulomb force to respiratory particles, powered by human body triboelectric energy harvesting. We show that SARS-CoV-2 has negative charges, and a human body generates high output current of which peak-to-peak value reaches 259.6 µA at most, based on triboelectric effect. Thereby, the human body can sustainably power a VBT to have negative electrical potential, and the VBT highly blocks SARS-CoV-2 by repulsion. In an acrylic chamber study, we found that the VBT blocks SARS-CoV-2 by 99.95%, and SARS-CoV-2 in the VBT is 13-fold reduced. Our work provides technology that may prevent the spread of virus based on repulsive Coulomb force and triboelectric energy harvesting.

Enhanced eosinophil-mediated inflammation associated with antibody and complement-dependent pneumonic insults in critical COVID-19.

Despite the worldwide effect of the coronavirus disease 2019 (COVID-19) pandemic, the underlying mechanisms of fatal viral pneumonia remain elusive. Here, we show that critical COVID-19 is associated with enhanced eosinophil-mediated inflammation when compared to non-critical cases. In addition, we confirm increased T helper (Th)2-biased adaptive immune responses, accompanying overt complement activation, in the critical group. Moreover, enhanced antibody responses and complement activation are associated with disease pathogenesis as evidenced by formation of immune complexes and membrane attack complexes in airways and vasculature of lung biopsies from six fatal cases, as well as by enhanced hallmark gene set signatures of Fcγ receptor (FcγR) signaling and complement activation in myeloid cells of respiratory specimens from critical COVID-19 patients. These results suggest that SARS-CoV-2 infection may drive specific innate immune responses, including eosinophil-mediated inflammation, and subsequent pulmonary pathogenesis via enhanced Th2-biased immune responses, which might be crucial drivers of critical disease in COVID-19 patients.

Application of ZnO-Based Nanocomposites for Vaccines and Cancer Immunotherapy.

Engineering and application of nanomaterials have recently helped advance various biomedical fields. Zinc oxide (ZnO)-based nanocomposites have become one of the most promising candidates for biomedical applications due to their biocompatibility, unique physicochemical properties, and cost-effective mass production. In addition, recent advances in nano-engineering technologies enable the generation of ZnO nanocomposites with unique three-dimensional structures and surface characteristics that are optimally designed for in vivo applications. Here, we review recent advances in the application of diverse ZnO nanocomposites, with an especial focus on their development as vaccine adjuvant and cancer immunotherapeutics, as well as their intrinsic properties interacting with the immune system and potential toxic effect in vivo. Finally, we summarize promising proof-of-concept applications as prophylactic and therapeutic vaccines against infections and cancers. Understanding the nano-bio interfaces between ZnO-based nanocomposites and the immune system, together with bio-effective design of the nanomaterial using nano-architectonic technology, may open new avenues in expanding the biomedical application of ZnO nanocomposites as a novel vaccine platform.

Application of radially grown ZnO nanowires on poly-l-lactide microfibers complexed with a tumor antigen for cancer immunotherapy.

Zinc oxide (ZnO)-based nanocomposites have shown promising potential for various biomedical applications, including vaccine development, owing to their multifunctionality and biocompatibility. Here, we synthesized radially grown ZnO nanowires (NWs) on poly-l-lactic acid (PLLA) microfibers with unique 3-dimensional structure and applied them as therapeutic cancer vaccines. This inorganic-organic hybrid nanocomposite has mild cellular toxicity but efficiently delivers a tumor antigen into dendritic cells, cellular bridges between innate and adaptive immunity, to stimulate them to express inflammatory cytokines and activation surface markers. We also demonstrated that the hybrid nanocomposites successfully induce tumor antigen-specific cellular immunity and significantly inhibit tumor growth in vivo. ZnO NWs on PLLA fibers systemically reduced immune suppressive TReg cells and enhanced the infiltration of T cells into tumor tissues, compared to mice immunized with PLLA fibers coated with the antigen. Our current findings open a new avenue in extending the biomedical application of inorganic metal oxide-inert organic hybrid nanocomposites as a novel vaccine platform.