A Computational Model of Cytokine Release Syndrome during CAR T‐Cell Therapy
A Computational Model of Cytokine Release Syndrome during CAR T‐Cell Therapy
复制标题
CAR T 细胞治疗过程中细胞因子释放综合征的计算模型
DOI：
10.1002/adtp.202200130
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发表时间：
2022
影响因子：
4.6
通讯作者：
Chen, Weiqiang
中科院分区：
文献类型：
--
作者：
Zhang, Zhuoyu;Liu, Lunan;Ma, Chao;Chen, Weiqiang
细胞因子释放综合征 (CRS) 是嵌合抗原受体 (CAR) T 细胞疗法中的致命不良事件，阻碍了这种有希望的癌症疗法，例如 B 细胞急性淋巴细胞白血病 (B-ALL)。 CRS 的临床管理需要更好地了解其潜在机制。在这项研究中，建立了 CAR T 细胞治疗期间 CRS 的计算模型，以描述 CAR T 细胞、B-ALL 细胞和旁观者单核细胞之间的细胞相互作用，以及各种炎症细胞因子之间伴随的分子相互作用如何影响 CRS 的严重程度。该模型成功定义了严重CRS的相关因素，并研究了免疫调节治疗对CRS的影响。该模型的使用也被证明是一种精准医疗工具，可优化治疗方案，包括个性化选择 CAR T 细胞产品和控制可切换的 CAR T 细胞活性，以实现更高效、更安全的免疫治疗。这种新的计算肿瘤学模型可以作为精准医学工具来指导 CAR T 细胞治疗期间 CRS 的临床管理。
Cytokine release syndrome (CRS) is a lethal adverse event in chimeric antigen receptor (CAR) T‐cell therapy, hindering this promising therapy for cancers, such as B‐cell acute lymphoblastic leukemia (B‐ALL). Clinical management of CRS requires a better understanding of its underlying mechanisms. In this study, a computational model of CRS during CAR T‐cell therapy is built to depict how the cellular interactions among CAR T‐cells, B‐ALL cells, and bystander monocytes, as well as the accompanying molecular interactions among various inflammatory cytokines, influence the severity of CRS. The model successfully defines the factors related to severe CRS and studies the effects of immunomodulatory therapy on CRS. The use of the model is also demonstrated as a precision medicine tool to optimize the treatment scheme, including personalized choice of CAR T‐cell products and control of switchable CAR T‐cell activity, for a more efficient and safer immunotherapy. This new computational oncology model can serve as a precision medicine tool to guide the clinical management of CRS during CAR T cell therapy.