Evaluation of an Adoptive Cellular Therapy-Based Vaccine in a Transgenic Mouse Model of α-synucleinopathy.
Evaluation of an Adoptive Cellular Therapy-Based Vaccine in a Transgenic Mouse Model of α-synucleinopathy.
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DOI：
10.1021/acschemneuro.2c00539
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发表时间：
2023-01-18
影响因子：
5
通讯作者：
Vedam-Mai, Vinata
中科院分区：
文献类型：
--
作者：
Chu, Winston T.;Hall, Jesse;Gurrala, Anjela;Becsey, Alexander;Raman, Shreya;Okun, Michael S.;Flores, Catherine T.;Giasson, Benoit I.;Vaillancourt, David E.;Vedam-Mai, Vinata
关键词：
聚集的α-突触核蛋白是路易体的主要成分，在帕金森病等α-突触核蛋白病的发病机制中起着重要作用。PD受免疫系统的先天性和适应性臂的影响，最近针对α-突触核蛋白的主动和被动免疫疗法都被试验作为潜在的新治疗策略。具体而言，基于树突状细胞的疫苗已被证明是动物模型中SP的有效治疗。在此，我们报告了SP过继细胞治疗（ACT）的发展，并证明过继转移免疫小鼠产生的预活化T细胞可改善存活率和行为，通过磁共振成像（MRI）减少脑微结构损伤，并在疾病发作前给药时，在外周诱导的临床前SP模型（M83）中降低α-突触核蛋白病理学负荷。本研究为ACT作为LBD、PD和其他相关SP的潜在免疫治疗提供了临床前证据，未来的工作将为其作用机制提供必要的了解。
Aggregated α-synuclein, a major constituent of Lewy bodies plays a crucial role in the pathogenesis of α-synucleinopathies (SPs) such as Parkinson’s disease (PD). PD is affected by the innate and adaptive arms of the immune system, and recently both active and passive immunotherapies targeted against α-synuclein are being trialed as potential novel treatment strategies. Specifically, dendritic cell-based vaccines have shown to be an effective treatment for SPs in animal models. Here, we report on the development of adoptive cellular therapy (ACT) for SP and demonstrate that adoptive transfer of pre-activated T-cells generated from immunized mice can improve survival and behavior, reduce brain microstructural impairment via magnetic resonance imaging (MRI), and decrease α-synuclein pathology burden in a peripherally induced preclinical SP model (M83) when administered prior to disease onset. This study provides preclinical evidence for ACT as a potential immunotherapy for LBD, PD and other related SPs, and future work will provide necessary understanding of the mechanisms of its action.
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影响因子：
16.2
作者：
Giasson, BI;Duda, JE;Lee, VMY
通讯作者：
Lee, VMY
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
8.8
作者：
Alam, Md Masud;Yang, De;Li, Xiao-Qing;Liu, Jia;Back, Timothy Carrel;Trivett, Anna;Karim, Baktiar;Barbut, Denise;Zasloff, Michael;Oppenheim, Joost J.
通讯作者：
Oppenheim, Joost J.
影响因子：
10.9
作者：
Avants, B. B.;Epstein, C. L.;Gee, J. C.
通讯作者：
Gee, J. C.
影响因子：
6.1
作者：
DeSimone, Jesse C.;Febo, Marcelo;Shukla, Priyank;Ofori, Edward;Colon-Perez, Luis M.;Li, Yuqing;Vaillancourt, David E.
通讯作者：
Vaillancourt, David E.