Polyanhydride nanoparticles stabilize pancreatic cancer antigen MUC4β.
Polyanhydride nanoparticles stabilize pancreatic cancer antigen MUC4β.
复制标题
聚酸酐纳米颗粒稳定胰腺癌抗原MUC4β。
DOI：
10.1002/jbm.a.37080
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Narasimhan B
中科院分区：
文献类型：
--
作者：
Liu L;Kshirsagar P;Christiansen J;Gautam SK;Aithal A;Gulati M;Kumar S;Solheim JC;Batra SK;Jain M;Wannemuehler MJ;Narasimhan B
胰腺癌（PC）是最致命的恶性肿瘤之一，是一个日益增长和具有挑战性的威胁，特别是随着人口老龄化。免疫原性pc特异性上调抗原的鉴定和对免疫抑制肿瘤微环境的进一步了解为免疫系统识别癌细胞提供了机会。由于其在PC中的差异上调和功能作用，跨膜粘蛋白MUC4是免疫治疗的一个有吸引力的靶点。在当前的研究中，我们对muc4 β纳米疫苗的抗原稳定性、抗原性和释放动力学进行了表征，以指导进一步的优化和体内评价。以20摩尔% 1,8-二（对羧基苯氧基）-3,6-二氧杂辛烷和80摩尔% 1,6-二（对羧基苯氧基）己烷为共聚物制备纳米颗粒。结构稳定的MUC4β蛋白从颗粒中持续释放，并通过凝胶电泳和荧光光谱对其进行了表征。释放后观察到适度水平的蛋白质降解。释放的蛋白也通过muc4 β特异性单克隆抗体使用ELISA进行分析，显示表位可用性没有明显损失。此外，用含有负载muc4 β纳米颗粒的多种组合疫苗免疫小鼠可产生muc4 β特异性抗体反应。这些结果表明，聚酸酐纳米颗粒是MUC4β疫苗可行的载体，为评价该平台用于PC免疫治疗奠定了基础。
Pancreatic cancer (PC) is one of the most lethal malignancies and represents an increasing and challenging threat, especially with an aging population. The identification of immunogenic PC-specific upregulated antigens and an enhanced understanding of the immunosuppressive tumor microenvironment have provided opportunities to enable the immune system to recognize cancer cells. Due to its differential upregulation and functional role in PC, the transmembrane mucin MUC4 is an attractive target for immunotherapy. In the current study we characterized the antigen stability, antigenicity and release kinetics of a MUC4β-nanovaccine to guide further optimization and, in vivo evaluation. Amphiphilic polyanhydride copolymers based on 20 mol % 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane and 80 mol % 1,6-bis(p-carboxyphenoxy)hexane were used to synthesize nanoparticles. Structurally stable MUC4β protein was released from the particles in a sustained manner and characterized by gel electrophoresis and fluorescence spectroscopy. Modest levels of protein degradation were observed upon release. The released protein was also analyzed by MUC4β-specific monoclonal antibodies using ELISA and showed no significant loss of epitope availability. Further, mice immunized with multiple formulations of combination vaccines containing MUC4β-loaded nanoparticles generated MUC4β-specific antibody responses. These results indicate that polyanhydride nanoparticles are viable MUC4β vaccine carriers, laying the foundation for evaluation of this platform for PC immunotherapy.
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影响因子：
3.7
作者：
Aithal A;Junker WM;Kshirsagar P;Das S;Kaur S;Orzechowski C;Gautam SK;Jahan R;Sheinin YM;Lakshmanan I;Ponnusamy MP;Batra SK;Jain M
通讯作者：
Jain M
影响因子：
--
作者：
Koido S;Homma S;Takahara A;Namiki Y;Tsukinaga S;Mitobe J;Odahara S;Yukawa T;Matsudaira H;Nagatsuma K;Uchiyama K;Satoh K;Ito M;Komita H;Arakawa H;Ohkusa T;Gong J;Tajiri H
通讯作者：
Tajiri H
影响因子：
62.1
作者：
Kamaly N;Yameen B;Wu J;Farokhzad OC
通讯作者：
Farokhzad OC
影响因子：
4.6
作者：
Horn A;Chakraborty S;Dey P;Haridas D;Souchek J;Batra SK;Lele SM
通讯作者：
Lele SM
影响因子：
6.3
作者：
Hinoda, Y;Ikematsu, Y;Yonezawa, S
通讯作者：
Yonezawa, S