Zheng Xixi, Zhang Shuo, Wu Haiting, Xia Jinghua, Zheng Ke, Wang Ying, Qin Yan
Department of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, P.R. China.
Oncol Lett. 2024 Oct 14;28(6):607. doi: 10.3892/ol.2024.14740. eCollection 2024 Dec.
T-cell receptor-engineered T-cell (TCR-T) immunotherapy is a promising approach for the treatment of solid tumors. However, TCR-T therapy can result in severe cytokine release syndrome (CRS), thus limiting its therapeutic application. The present study reported the case of a patient with TCR-T-related CRS, which was treated successfully with plasma exchange (PE). A 35-year-old male patient, who was diagnosed with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) with lung metastases, was enrolled in a clinical trial for hepatitis B virus surface antigen-specific TCR-expressing autologous T-cell therapy for HBV-related HCC after failing multiple lines of targeted immunotherapy and local treatments. Therefore, TCR-Ts were infused after peripheral blood mononuclear cell collection, engineering and lymphodepletion chemotherapy. However, following engineered T-cell reinfusion, the patient developed a fever, hypotension, edema, multiple serous effusion and acute kidney injury, and was consequently diagnosed with grade 3 CRS and transferred to the Intensive Care Unit. The patient received three daily PE sessions (3,000 ml of fresh frozen plasma per session), renal replacement therapy, tocilizumab and 1,000 mg pulse methylprednisolone for 3 days. Following treatment, the patient's hemodynamic condition was stabilized and the C-reactive protein, ferritin and IL-6 levels were markedly reduced. During follow-up, a stable disease state was exhibited by the liver cancer and lung metastatic lesions. To the best of our knowledge, this is the first case reporting PE as a treatment approach for managing CRS following TCR-T therapy for solid tumors. The present study demonstrated that blood purification treatments, such as PE, which target inflammatory mediators and restore the balance between pro- and anti-inflammatory cytokines, could be a notable component in managing severe CRS associated with engineered T-cell treatment. However, additional clinical and translational studies are needed to further understand the mechanisms of T-cell immunotherapy to treat patients with solid tumors.
T细胞受体工程化T细胞（TCR-T）免疫疗法是一种治疗实体瘤的有前景的方法。然而，TCR-T疗法可导致严重的细胞因子释放综合征（CRS），从而限制了其治疗应用。本研究报告了一例TCR-T相关CRS患者，该患者通过血浆置换（PE）成功治愈。一名35岁男性患者，被诊断为乙型肝炎病毒（HBV）相关肝细胞癌（HCC）伴肺转移，在多线靶向免疫治疗和局部治疗失败后，参加了一项针对HBV相关HCC的乙型肝炎病毒表面抗原特异性TCR表达自体T细胞治疗的临床试验。因此，在采集外周血单核细胞、进行工程改造和淋巴细胞清除化疗后，输注TCR-T细胞。然而，在回输工程化T细胞后，患者出现发热、低血压、水肿、多处浆液性积液和急性肾损伤，因此被诊断为3级CRS并转入重症监护病房。患者接受了每日3次的PE治疗（每次3000ml新鲜冰冻血浆）、肾脏替代治疗、托珠单抗和1000mg脉冲甲基强的松龙治疗3天。治疗后，患者的血流动力学状况稳定，C反应蛋白、铁蛋白和IL-6水平显著降低。随访期间，肝癌和肺转移病灶呈现疾病稳定状态。据我们所知，这是首例报告将PE作为实体瘤TCR-T治疗后CRS管理的治疗方法的病例。本研究表明，以炎症介质为靶点并恢复促炎细胞因子和抗炎细胞因子之间平衡的血液净化治疗，如PE，可能是管理与工程化T细胞治疗相关的严重CRS的一个重要组成部分。然而，需要更多的临床和转化研究来进一步了解T细胞免疫疗法治疗实体瘤患者的机制。
