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WIREs Nanomed Nanobiotechnol
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Biogenic nanoparticles as immunomodulator for tumor treatment

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Abstract In the past few decades, cancer immunotherapy has developed rapidly. Cancer immunotherapy, either used alone or in combination with a variety of immunotherapies (such as cancer therapeutic vaccines, adoptive cell therapy, or immune checkpoint blocking therapy), is a very attractive class of cancer therapy. However, so far, the clinical effect of most cancer immunotherapy is not satisfactory. It has been widely recognized that nanotechnology can enhance the efficacy of cancer immunotherapy. A variety of biogenic nanoparticles have been developed, which have excellent immunogenicity and modifiability, and can carry tumor therapeutic drugs to achieve combined therapy, so as to improve the effectiveness and durability of antitumor immunity while reducing adverse side effects. In this review, we summarized the key parameters and futures of three kinds of biogenic nanomaterials in cancer immunotherapy; we highlighted the progress of cancer immunotherapy based on outer membrane vesicles, virus‐like particles, and exosomes. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Biogenesis, antigens decoration methods, and immune response of OMVs. (a) Biogenesis of OMV production in bacteria. Figure depicts the composition of OMV, cargo selection, and loading as part of OMVs (Jan, 2017). (b) Methods of antigen decoration on OMVs. Top row shows surface exposed antigens on the vesicles, bottom row shows the antigens as luminal cargo of OMVs. Antigens can be produced by the OMV production bacterium (left), while antigen addition to purified vesicles can be divided in mixing, conjugation, and encapsulation (middle and right) (Gerritzen, Martens, Wijffels, van der Pol, & Stork, 2017). (c) and (d) innate immunity induced by OMVs in vivo. (c) Tumor volume of mice bearing CT26 murine colon adenocarcinoma measured after E. coli ΔmsbB OMV treatments with various amounts (total n = 14 mice per group, two independent experiments). E. coli ΔmsbB OMVs were injected intravenously four times from Day 6 with 3‐day intervals. (d) Picture of mice bearing tumor after PBS or ΔmsbB OMV (5 μg in total protein amount) treatments. Yellow box indicates tumor sites (O. Y. Kim, Park, et al., 2017). OMVs, outer membrane vesicles
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Exosomes for tumor immunotherapy. (a) Biogenesis of exosomes. Exosomes are represented by small vesicles of different sizes that are formed as the ILV by budding into early endosomes and MVEs and are released by fusion of MVEs with the plasma membrane (Raposo & Stoorvogel, 2013). (b) Schematic of the design and generation of αCD3/αEGFR synthetic multivalent antibodies retargeted exosomes (SMART‐Exos). SMART‐Exos were shown to not only induce cross‐linking of T cells and EGFR‐expressing breast cancer cells but also elicit potent antitumor immunity both in vitro and in vivo (Chen et al., 2018)
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VLPs can enhance cancer immunotherapy. (a) Putative mechanisms of VLP‐mediated stimulation of innate and adaptive immune responses. VLPs can promote the maturation of DCs. Matured DCs present VLP‐derived antigens to naive CD4+ and CD8+ T cells via MHC Class I and Class II. Secretion of cytokines by DCs stimulates differentiation into B and T effector cells resulting in antibody release and cytotoxic T cell (CTL) responses (Ludwig & Wagner, 2007). (b) Overview of plug‐and‐display VLP assembly. SpyCatcher is genetically fused to the AP205 phage coat protein (AP205 CP3) and expressed in E. coli. Self‐assembly of monomers generates SpyCatcher‐VLPs. Upon mixing, SpyTag‐antigen forms a spontaneous isopeptide bond with SpyCatcher‐VLPs, yielding decorated particles for immunization (Brune et al., 2016). DCs, dendritic cells; VLPs, virus‐like particles
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Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

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