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Polyelectrolyte‐Enrobed Cancer Cells in View of Personalized Immune‐Therapy

机译:鉴于个性化免疫疗法聚电解质包裹的癌细胞

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摘要

Targeting the immune system with a personalized vaccine containing cues derived from the patient's malignancy might be a promising approach in the fight against cancer. It includes neo‐antigens as well as nonmutated tumor antigens, preferentially leading to an immune response that is directed to a broader range of epitopes compared to strategies involving a single antigen. Here, this paper reports on an elegant method to encapsulate whole cancer cells into polyelectrolyte particles. Porous and nonaggregated microparticles containing dead cancer cells are obtained by admixing mannitol and live cancer cells with oppositely charged polyelectrolytes, dextran sulfate (anionic polysaccharide), and poly‐l‐arginine (cationic polypeptide) prior to atomization into a hot air stream. It shows that the polyelectrolyte‐enrobed cancer cells, upon redispersion in phosphate buffered saline buffer, are stable and do not release cell proteins in the supernatant. In vitro experiments reveal that the particles are nontoxic and strongly increase uptake of cell lysate by dendritic cells. In vitro assessment of antigen presentation by dendritic cells reveal the potential of the polyelectrolyte‐enrobed cancer cells as promotors of antigen cross‐presentation. Finally, it is demonstrated that the immunogenicity can be enhanced by surface adsorption of a polymer‐substituted TLR7‐agonist.
机译:用包含来自患者恶性肿瘤的线索的个性化疫苗靶向免疫系统可能是抗击癌症的一种有前途的方法。它包括新抗原以及未突变的肿瘤抗原,与涉及单个抗原的策略相比,它优先导致针对更广泛表位的免疫反应。在此,本文报道了一种将整个癌细胞封装为聚电解质颗粒的绝佳方法。通过将甘露醇和活癌细胞与带相反电荷的聚电解质,硫酸葡聚糖(阴离子多糖)和聚-1-精氨酸(阳离子多肽)混合,然后雾化成热气流,即可获得含有死亡癌细胞的多孔且未聚集的微粒。结果表明,聚电解质包裹的癌细胞在磷酸盐缓冲液中重新分散后是稳定的,不会在上清液中释放细胞蛋白。体外实验表明,该颗粒无毒,并且会强烈增加树突状细胞对细胞裂解液的摄取。树突状细胞对抗原呈递的体外评估显示,聚电解质包裹的癌细胞具有促进抗原交叉呈递的潜力。最后,证明了通过聚合物取代的TLR7激动剂的表面吸附可以增强免疫原性。

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