SARS-CoV-2-specific T cells are rapidly expanded for therapeutic use and target conserved regions of the membrane protein.
SARS-CoV-2-specific T cells are rapidly expanded for therapeutic use and target conserved regions of the membrane protein.
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SARS-COV-2特异性T细胞迅速扩展以供治疗用途，并靶向保守的膜蛋白。
DOI：
10.1182/blood.2020008488
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发表时间：
2020-12-17
期刊：
影响因子：
20.3
通讯作者：
Bollard CM
中科院分区：
文献类型：
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作者：
Keller MD;Harris KM;Jensen-Wachspress MA;Kankate VV;Lang H;Lazarski CA;Durkee-Shock J;Lee PH;Chaudhry K;Webber K;Datar A;Terpilowski M;Reynolds EK;Stevenson EM;Val S;Shancer Z;Zhang N;Ulrey R;Ekanem U;Stanojevic M;Geiger A;Liang H;Hoq F;Abraham AA;Hanley PJ;Cruz CR;Ferrer K;Dropulic L;Gangler K;Burbelo PD;Jones RB;Cohen JI;Bollard CM
出版商注：本期此文章有一处[此处可能缺失信息]。
从康复个体中可扩增出针对新冠病毒的多功能T细胞，用于骨髓移植后的患者。
新冠病毒（SARS - CoV - 2）的T细胞产物靶向病毒结构蛋白，包括膜蛋白C末端常见的识别区域。
在康复患者中已发现对严重急性呼吸综合征冠状病毒2（SARS - CoV - 2）的T细胞反应，这对于感染和接种疫苗后的免疫以及开发用于治疗免疫功能低下个体的过继性免疫疗法可能很重要。在本报告中，我们证明可以从康复供体中扩增出SARS - CoV - 2特异性T细胞，并且这些细胞能识别膜蛋白、刺突蛋白和核衣壳保守区域的免疫优势病毒表位。使用符合药品生产质量管理规范的方法（旨在使这种新型SARS - CoV - 2 T细胞疗法能够快速应用于临床）进行体外扩增后，膜蛋白、刺突蛋白和核衣壳肽分别在27名（59%）、12名（26%）和10名（22%）康复供体以及15名未暴露对照中的2名中诱导产生干扰素 - γ。我们在膜蛋白的一个高度保守区域内鉴定出多个受CD4限制的多功能T细胞表位，这些表位诱导了多功能T细胞反应，这对于开发有效的疫苗和T细胞疗法可能至关重要。因此，我们的研究表明，针对结构蛋白（最重要的是膜蛋白）的SARS - CoV - 2导向的T细胞免疫疗法对于预防或早期治疗患有血液疾病的免疫功能低下患者或骨髓移植后的SARS - CoV - 2感染应该是可行的，以实现抗病毒控制同时减轻不受控制的炎症。
Publisher's Note: There is a on this article in this issue. Coronavirus-specific polyfunctional T cells can be expanded from convalescent individuals for use for patients after bone marrow transplant. SARS-CoV-2 T-cell products target structural viral proteins, including commonly recognized regions in the C terminus of membrane protein. T-cell responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been described in recovered patients, and may be important for immunity following infection and vaccination as well as for the development of an adoptive immunotherapy for the treatment of immunocompromised individuals. In this report, we demonstrate that SARS-CoV-2–specific T cells can be expanded from convalescent donors and recognize immunodominant viral epitopes in conserved regions of membrane, spike, and nucleocapsid. Following in vitro expansion using a good manufacturing practice-compliant methodology (designed to allow the rapid translation of this novel SARS-CoV-2 T-cell therapy to the clinic), membrane, spike, and nucleocapsid peptides elicited interferon-γ production, in 27 (59%), 12 (26%), and 10 (22%) convalescent donors (respectively), as well as in 2 of 15 unexposed controls. We identified multiple polyfunctional CD4-restricted T-cell epitopes within a highly conserved region of membrane protein, which induced polyfunctional T-cell responses, which may be critical for the development of effective vaccine and T-cell therapies. Hence, our study shows that SARS-CoV-2 directed T-cell immunotherapy targeting structural proteins, most importantly membrane protein, should be feasible for the prevention or early treatment of SARS-CoV-2 infection in immunocompromised patients with blood disorders or after bone marrow transplantation to achieve antiviral control while mitigating uncontrolled inflammation.