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Abstract Immune checkpoint inhibitors (ICIs) represent new therapeutic candidates against glioblastoma multiforme (GBM); however, their efficacy is clinically limited due to both local and systemic immunosuppressive environments. Hence, therapeutic approaches that stimulate local and systemic immune environments can improve the efficacy of ICIs. Here, we report an adoptive cell therapy employing neutrophils (NE) that are activated via surface attachment of drug‐free disk‐shaped backpacks, termed Cyto‐Adhesive Micro‐Patches (CAMPs) for treating GBM. CAMP‐adhered neutrophils (NE/CAMPs) significantly improved the efficacy of an anti‐PD1 antibody (aPD‐1) in a subcutaneous murine GBM model (GL261). A combination of NE/CAMPs and aPD‐1 completely regressed subcutaneous GL261 tumors in mice. The efficacy of NE/CAMPs against GBM was also tested in an orthotopic GL261 model. Neutrophil's ability to migrate into the brain was not affected by CAMP attachment, and intracerebral NE/CAMP accumulation was observed in mice‐bearing orthotopic GBM. The combination treatment of NE/CAMPs and aPD‐1 activated systemic immune responses mediated by T cells and showed improved therapeutic responses compared with aPD‐1 alone in the orthotopic GBM model. These results suggest that immunomodulation with NE/CAMPs offers a potential approach for the treatment of GBM by combination with ICIs.

Abstract Vaccines are an important tool in the rapidly evolving repertoire of immunotherapies in oncology. Although cancer vaccines have been investigated for over 30 years, very few have achieved meaningful clinical success. However, recent advances in areas such antigen identification, formulation development and manufacturing, combination therapy regimens, and indication and patient selection hold promise to reinvigorate the field. Here, we provide a timely update on the clinical status of cancer vaccines. We identify and critically analyze 360 active trials of cancer vaccines according to delivery vehicle, antigen type, indication, and other metrics, as well as highlight eight globally approved products. Finally, we discuss current limitations and future applications for clinical translation of cancer vaccines.

Abstract Monoclonal antibodies that target SARS-CoV-2 with high affinity are valuable for a wide range of biomedical applications involving novel coronavirus disease (COVID-19) diagnosis, treatment, and prophylactic intervention. Strategies for the rapid and reliable isolation of these antibodies, especially potent neutralizing antibodies, are critical toward improved COVID-19 response and informed future response to emergent infectious diseases. In this study, single B cell screening was used to interrogate antibody repertoires of immunized mice and isolate antigen-specific IgG1+ memory B cells. Using these methods, high-affinity, potent neutralizing antibodies were identified that target the receptor-binding domain of SARS-CoV-2. Further engineering of the identified molecules to increase valency resulted in enhanced neutralizing activity. Mechanistic investigation revealed that these antibodies compete with ACE2 for binding to the receptor-binding domain of SARS-CoV-2. These antibodies may warrant further development for urgent COVID-19 applications. Overall, these results highlight the potential of single B cell screening for the rapid and reliable identification of high-affinity, potent neutralizing antibodies for infectious disease applications.

Abstract Nanoparticles (NPs) can serve as a promising vaccine delivery platform for improving pharmacological property and codelivery of antigens and adjuvants. However, NP‐based vaccines are generally associated with complex synthesis and postmodification procedures, which pose technical and manufacturing challenges for tailor‐made vaccine production. Here, modularly programmed, polyethyleneimine (PEI)‐based NP vaccines are reported for simple production of personalized cancer vaccines. Briefly, PEI is conjugated with neoantigens by facile coupling chemistry, followed by electrostatic assembly with CpG adjuvants, leading to the self‐assembly of nontoxic, sub‐50 nm PEI NPs. Importantly, PEI NPs promote activation and antigen cross‐presentation of antigen‐presenting cells and cross‐priming of neoantigen‐specific CD8+ T cells. Surprisingly, after only a single intratumoral injection, PEI NPs with optimal PEGylation elicit as high as ≈30% neoantigen‐specific CD8+ T cell response in the systemic circulation and sustain elevated CD8+ T cell response over 3 weeks. PEI‐based nanovaccines exert potent antitumor efficacy against pre‐established local tumors as well as highly aggressive metastatic tumors. PEI engineering for modular incorporation of neoantigens and adjuvants offers a promising strategy for rapid and facile production of personalized cancer vaccines.

BackgroundRecent studies have shown the importance of postprandial glucose (PPG) in the development of diabetes complications. This study was conducted in order to survey the perceptions of clinicians and diabetic patients with respect to PPG management and the current status of diabetes education.MethodsThis was a cross-sectional study involving face-to-face interviews and an open questionnaire survey conducted in Korea. A total of 300 patients and 130 clinicians completed questionnaires, which included current education status, self monitoring of blood glucose (SMBG), criteria of diagnosis and management, and perceptions relating to PPG management.ResultsWhile there was a significantly higher perceived need for diabetes education, the sufficiency of the current education was considered to be severely lacking. Fasting plasma glucose (FPG), PPG, and glycosylated hemoglobin (HbA1c) were all important considerations for clinicians when making a diagnosis of diabetes, although PPG was considered less important than FPG or HbA1c in the treatment of diabetes. Most clinicians and patients were aware of the importance of PPG, but actual education on the importance of PPG was not actively being delivered.ConclusionOur study showed that the current status of diabetes education is insufficient to meet the needs of the Korean population. A considerable gap was found to exist between awareness and what was actually taught in the current education program in regard to the importance of PPG. These results suggest that clinicians need to be more active in patient education, especially in regard to the importance of PPG.

Doping and hybridization with other semiconductors are highly effective ways to address the limitations, including their weak response to visible light and significant recombination of photogenerated carriers. In addition, the assisted carbon on the catalyst surface and the structural design have the advantage of being catalytically active. Herein, visible-light-active N-doped C/Na2Ti6O13/TiO2 hollow spheres (denoted as N–C/NTO/TiO2 HS) were successfully prepared using a facile two-step method and evaluated for methylene blue (MB) aqueous solution degradation under visible-light irradiation.The as-obtained N–C/NTO/TiO2 HS demonstrated improved photocatalytic efficiency (94 %) and pseudo-first-order kinetic degradation rate (0.023 min−1). Moreover, after three cycles of testing, N–C/NTO/TiO2 HS showed a 91 % degradation rate in its photostability. The enhanced photocatalytic performance was attributed to the combined effects of N-doping, carbon species on the surface, and the coupling of TiO2 and Na2Ti6O13 using morphology engineering. Finally, based on the experimental results, a possible photocatalytic mechanism was proposed. This study provides a rational approach toward the development of high-performance titanate-based photocatalysts for solar energy-assisted wastewater treatment.

Abstract Background Nanoparticles have been used for biomedical applications, including drug delivery, diagnosis, and imaging based on their unique properties derived from small size and large surface-to-volume ratio. However, concerns regarding unexpected toxicity due to the localization of nanoparticles in the cells are growing. Herein, we quantified the number of cell-internalized nanoparticles and monitored their cellular localization, which are critical factors for biomedical applications of nanoparticles. Methods This study investigates the intracellular trafficking of silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye [MNPs@SiO2(RITC)] in various live single cells, such as HEK293, NIH3T3, and RAW 264.7 cells, using site-specific direct stochastic optical reconstruction microscopy (dSTORM). The time-dependent subdiffraction-limit spatial resolution of the dSTORM method allowed intracellular site-specific quantification and tracking of MNPs@SiO2(RITC). Results The MNPs@SiO2(RITC) were observed to be highly internalized in RAW 264.7 cells, compared to the HEK293 and NIH3T3 cells undergoing single-particle analysis. In addition, MNPs@SiO2(RITC) were internalized within the nuclei of RAW 264.7 and HEK293 cells but were not detected in the nuclei of NIH3T3 cells. Moreover, because of the treatment of the MNPs@SiO2(RITC), more micronuclei were detected in RAW 264.7 cells than in other cells. Conclusion The sensitive and quantitative evaluations of MNPs@SiO2(RITC) at specific sites in three different cells using a combination of dSTORM, transcriptomics, and molecular biology were performed. These findings highlight the quantitative differences in the uptake efficiency of MNPs@SiO2(RITC) and ultra-sensitivity, varying according to the cell types as ascertained by subdiffraction-limit super-resolution microscopy. Graphical Abstract

While primaquine has long been used for malaria treatment, treatment failure is common. This study aims to develop a population pharmacokinetic model of primaquine and its metabolite, carboxyprimaquine, and examine factors influencing pharmacokinetic variability. The data was obtained from a clinical study in 24 Korean subjects randomly assigned to normal and obese groups. The participants received primaquine 15 mg daily for 4 days and blood samples were collected at day 4. Pharmacokinetic modeling was performed with NONMEM and using simulations; the influences of doses and covariates on drug exposure were examined. A minimal physiology-based pharmacokinetic model connected with a liver compartment comprehensively described the data, with CYP450 mediated clearance being positively correlated with the body weight and CYP2D6 activity score (p < 0.05). In the simulation, while the weight-normalized area under drug concentration for primaquine in the obese group decreased by 29% at the current recommended dose of 15 mg, it became similar to the normal weight group at a weight-normalized dose of 3.5 mg/kg. This study has demonstrated that the body weight and CYP2D6 activity score significantly influence the pharmacokinetics of primaquine. The developed model is expected to be used as a basis for optimal malaria treatment in Korean patients.