We report a method of inducing antigen production in dendritic cells (DCs) by in vivo targeting with lentiviral vectors that specifically bind to the DC surface protein, DC-SIGN. To target the DCs, the lentivector was enveloped with a viral glycoprotein from Sindbis virus, engineered to be DC-SIGNspecific. In vitro, this lentivector specifically transduced DCs and induced DC maturation. A remarkable frequency (up to 12%) of ovalbumin (OVA)-specific CD8 + T cells and a significant antibody response were observed 2 weeks following injection of a targeted lentiviral vector encoding an OVA transgene into naïve mice. These mice were solidly protected against the growth of the OVA-expressing E.G7 tumor and this methodology could even induce regression of an established tumor. Thus, lentiviral vectors targeting DCs provide a simple method of producing effective immunity and may provide an alternative route for immunization with protein antigens.Immunization is one of the most productive tools in modern medical practice yet it still has limitations and novel methods of immunization are likely to be needed. 1 One of the great advances in our understanding of the process of immunization was the recognition of the role of dendritic cells (DCs) as specialized antigen-presenting cells (APCs). 2 This has led to attempts at DC-based immunization/vaccination involving loading DCs with specific antigens. 3, 4 Although significant progress has been made on various aspects of this vaccination method, many challenges still remain in order to rationally manipulate DCs to achieve protective immunity. [3][4][5] There is growing interest in genetically modifying DCs to make them either express antigens or produce immuno-stimulatory molecules. 6 Of these methods, viral vectors have been proven most effective for the delivery of genes into DCs in vitro. 7 The most popular viral vectors capable of transducing and expressing transgenes in DCs are adenoviral vectors, 8-10 gammaretroviral vectors 11, 12 and lentiviral vectors. [13][14][15] Considerable effort has also gone towards direct immunization using recombinant viral vectors as vaccine carriers. In these protocols, viral vectors are injected directly into an animal with the hope that a fraction will target immune cells and stimulate the desired immunity. Direct injection of adenoviral vectors was shown to induce both innate and adaptive immune responses and is currently being evaluated as a subunit vaccine for several infectious diseases and cancer. 16-18 Direct injection of lentivectors into mice does transduce DCs, leading to antigen-specific CD8 + T cell responses and anti-tumor immunity. 19-22 However, these 4Correspondence should be addressed to D.B. (baltimo@caltech.edu) or P.W. (pinwang@usc.edu). 3 These authors contribute equally to this work. COMPETING INTERESTS STATEMENT:The authors declare that they have no competing financial interests. Here we report a new method of in vivo DC targeting through the DC-specific surface molecule called DC-SIGN (also known as CD209) ...

Shortage of face masks is a current critical concern since the emergence of coronavirus-2 or SARS- . In this work, we compared the melt-blown (MB) filter, which is commonly used for the N95 face mask, with nanofiber (NF) filter, which is gradually used as an effective mask filter, to evaluate their reusability. Extensive characterizations were performed repeatedly to evaluate some performance parameters, which include filtration efficiency, airflow rate, and surface and morphological properties, after two types of cleaning treatments. In the first cleaning type, samples were dipped in 75% ethanol for a predetermined duration. In the second cleaning type, 75% ethanol was sprayed on samples. It was found that filtration efficiency of MB filter was significantly dropped after treatment with ethanol, while the NF filter exhibited consistent high filtration efficiency regardless of cleaning types. In addition, the NF filter showed better cytocompatibility than the MB filter, demonstrating its harmlessness on the human body. Regardless of ethanol treatments, surfaces of both filter types maintained hydrophobicity, which can sufficiently prevent wetting by moisture and saliva splash to prohibit not only pathogen transmission but also bacterial growth inside. On the basis of these comparative evaluations, the wider use of the NF filter for face mask applications is highly recommended, and it can be reused multiple times with robust filtration efficiency. It would be greatly helpful to solve the current shortage issue of face masks and significantly improve safety for front line fighters against coronavirus disease.

No abstract

Liposomes constitute one of the most popular nanocarriers for the delivery of cancer therapeutics. However, since their potency is limited by incomplete drug release and inherent instability in the presence of serum components, their poor delivery occurs in certain circumstances. In this study, we address these shortcomings and demonstrate an alternative liposomal formulation, termed crosslinked multilamellar liposome (CML). With its properties of improved sustainable drug release kinetics and enhanced vesicle stability, CML can achieve controlled delivery of cancer therapeutics. CML stably encapsulated the anticancer drug doxorubicin (Dox) in the vesicle and exhibited a remarkably controlled rate of release compared to that of the unilamellar liposome (UL) with the same lipid composition or Doxil-like liposome (DLL). Our imaging study demonstrated that the CMLs were mainly internalized through a caveolin-dependent pathway and were further trafficked through the endosome-lysosome compartments. Furthermore, in vivo experiments showed that the CML-Dox formulation reduced systemic toxicity and significantly improved therapeutic activity in inhibiting tumor growth compared to that of UL-Dox or DLL-Dox. This drug packaging technology may therefore provide a new treatment option to better manage cancer and other diseases.

Fibroblast activation protein (FAP) is highly expressed in the tumor-associated fibroblasts (TAFs) of most human epithelial cancers. FAP plays a critical role in tumorigenesis and cancer progression, which makes it a promising target for novel anticancer therapy. However, mere abrogation of FAP enzymatic activity by small molecules is not very effective in inhibiting tumor growth. In this study, we have evaluated a novel immune-based approach to specifically deplete FAP-expressing TAFs in a mouse 4T1 metastatic breast cancer model. Depletion of FAP-positive stromal cells by FAP-targeting immunotoxin αFAP-PE38 altered levels of various growth factors, cytokines, chemokines and matrix metalloproteinases, decreased the recruitment of tumor infiltrating immune cells in the tumor microenvironment and suppressed tumor growth. In addition, combined treatment with αFAP-PE38 and paclitaxel potently inhibited tumor growth in vivo. Our findings highlight the potential use of immunotoxin αFAP-PE38 to deplete FAP-expressing TAFs and thus provide a rationale for the use of this immunotoxin in cancer therapy.