Case Report: Clinical and Serological Hallmarks of Cytokine Release Syndrome in a Canine B Cell Lymphoma Patient Treated With Autologous CAR-T Cells.
Case Report: Clinical and Serological Hallmarks of Cytokine Release Syndrome in a Canine B Cell Lymphoma Patient Treated With Autologous CAR-T Cells.
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DOI：
10.3389/fvets.2022.824982
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发表时间：
2022
影响因子：
3.2
通讯作者：
中科院分区：
文献类型：
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作者：
嵌合抗原受体-T（CAR-T）细胞已经改变了人类B细胞恶性肿瘤的治疗。随着CAR-T疗法的出现，已经记录了特定的和在某些情况下严重的毒性，其中细胞因子释放综合征（CRS）是最常报告的。由于犬在免疫活性环境中自发发生肿瘤，因此它们提供了一个独特的转化机会，以进一步研究与CAR-T治疗相关的活性和毒性。虽然已经记录了各种过继细胞治疗（ACT）试验，并且还有几项正在犬肿瘤学中进行，但CRS尚未在犬癌症患者中进行全面描述。在这里，我们介绍了一只接受自体CAR-T治疗复发性B细胞淋巴瘤的犬的临床和血清学变化，该犬在CAR-T后3天出现嗜睡和发热。多重血清细胞因子分析显示，在体内峰值CAR-T水平时或峰值CAR-T水平后不久，与人CRS相关的关键细胞因子（包括IL-6、MCP-1、IFNγ和IL-10）增加。本病例报告中的观察结果与犬患者接受CAR-T治疗后的CRS发展一致。狗代表了一个令人信服的模型来研究CRS的病理生理学和临床前筛选新的治疗方法，以预防和治疗这种危及生命的疾病，在复杂和自然进化的免疫系统的设置。
Chimeric antigen receptor-T (CAR-T) cells have transformed the treatment of human B cell malignancies. With the advent of CAR-T therapy, specific and in some cases severe toxicities have been documented with cytokine release syndrome (CRS) being the most frequently reported. As dogs develop tumors spontaneously and in an immunocompetent setting, they provide a unique translational opportunity to further investigate the activity and toxicities associated with CAR-T therapy. Although various adoptive cellular therapy (ACT) trials have been documented and several more are ongoing in canine oncology, CRS has not been comprehensively described in canine cancer patients. Here we present the clinical and serologic changes in a dog treated with autologous CAR-T for relapsed B cell lymphoma that presented with lethargy and fever 3 days following CAR-T. Multiplexed serum cytokine profiling revealed increases in key cytokines implicated in human CRS including IL-6, MCP-1, IFNγ and IL-10 at or shortly after peak CAR-T levels in vivo. The observations noted in this case report are consistent with CRS development following CAR-T therapy in a canine patient. The dog represents a compelling model to study the pathophysiology of CRS and pre-clinically screen novel therapeutics to prevent and treat this life-threatening condition in the setting of a complex and naturally evolved immune system.
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DOI：
10.1056/nejmoa1707447
发表时间：
2017-12-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Neelapu SS;Locke FL;Bartlett NL;Lekakis LJ;Miklos DB;Jacobson CA;Braunschweig I;Oluwole OO;Siddiqi T;Lin Y;Timmerman JM;Stiff PJ;Friedberg JW;Flinn IW;Goy A;Hill BT;Smith MR;Deol A;Farooq U;McSweeney P;Munoz J;Avivi I;Castro JE;Westin JR;Chavez JC;Ghobadi A;Komanduri KV;Levy R;Jacobsen ED;Witzig TE;Reagan P;Bot A;Rossi J;Navale L;Jiang Y;Aycock J;Elias M;Chang D;Wiezorek J;Go WY
通讯作者：
Go WY
影响因子：
82.9
作者：
Giavridis T;van der Stegen SJC;Eyquem J;Hamieh M;Piersigilli A;Sadelain M
通讯作者：
Sadelain M
影响因子：
28.2
作者：
Taraseviciute A;Tkachev V;Ponce R;Turtle CJ;Snyder JM;Liggitt HD;Myerson D;Gonzalez-Cuyar L;Baldessari A;English C;Yu A;Zheng H;Furlan SN;Hunt DJ;Hoglund V;Finney O;Brakke H;Blazar BR;Berger C;Riddell SR;Gardner R;Kean LS;Jensen MC
通讯作者：
Jensen MC
影响因子：
82.9
作者：
Norelli, Margherita;Camisa, Barbara;Bondanza, Attilio
通讯作者：
Bondanza, Attilio
影响因子：
2.7
作者：
Ruetgen, Barbara C.;Hammer, Sabine E.;Saalmueller, Armin
通讯作者：
Saalmueller, Armin