肿瘤细胞治疗研究
英文原题：Case report: Differential diagnosis of highly amplified anti-CD5 CAR T cells and relapsed lymphoma cells in a patient with refractory ALK positive anaplastic large cell lymphoma.
这些结果表明抗CD5 CAR-T细胞可在r/r ALK+ ALCL患者中诱导临床反应。此外，本病例强调了在CAR-T细胞治疗的临床实验室诊断和预后中，利用高灵敏度和高准确度的先进技术进行生物学检测的重要性。
间变性大细胞淋巴瘤（ALCL）是T细胞淋巴瘤最常见的亚型之一。其中，难治性和复发性（r/r）ALK阳性ALCL缺乏有效疗法。嵌合抗原受体修饰的T（CAR-T）细胞疗法作为该疾病的治疗策略具有巨大前景。然而，目前尚不清楚抗CD5 CAR-T细胞是否足以对复发性ALK+ ALCL进行根治性治疗，也不清楚在CAR-T治疗期间基于实验室的准确诊断的作用。病例介绍：该青少年患者接受了含有编码CD5特异性VH结构域序列的自体T细胞。输注后，外周血中CAR-T细胞的拷贝数和比例均增加。患者的IL-6和铁蛋白水平出现显著波动，治疗后分别较基线升高13倍和70倍。此外，还观察到不良反应，包括4级皮疹、1级头痛、恶心和颈部疼痛。令人意外的是，根据PET/CT结果和腹股沟淋巴结活检的组织病理学分析，发现了复发性疾病表型。在进行全面的诊断评估后，包括流式细胞术、下一代测序（NGS）、免疫相关基因重排检查以及T细胞受体（TCR）免疫组库分析，我们最终确定淋巴结中发现的增生性T细胞是CAR-T细胞扩增的结果。最终，患者已达到完全缓解（CR），截至2023年8月30日的数据截止日期，已维持无病生存状态815天。
BACKGROUND: Anaplastic Large Cell Lymphoma (ALCL) is one of the most common subtypes of T-cell lymphoma. Among these, refractory and relapsed (r/r) ALK positive ALCL lacks effective therapies. The chimeric antigen receptor-modified T (CAR-T) cell therapy holds great promise as a therapeutic strategy for this disease. However, it is not known yet whether anti-CD5 CAR-T cells are sufficient for the definitive treatment of relapsed ALK + ALCL, nor the role of accurate laboratory-based diagnoses during CAR-T treatment. CASE PRESENTATION: The adolescent patient received autologous T cells containing sequences encoding V H domains specific to CD5. Following the infusion, there was an increase in both the copy number and proportion of CAR-T cells in peripheral blood. IL-6 and ferritin levels in the patient exhibited significant fluctuations, with increases of 13 and 70 folds respectively, compared to baseline after the treatment. Additionally, adverse effects were observed, including grade 4 rash, grade 1 headache, nausea, and neck-pain. Surprisingly, a relapsed disease phenotype was identified based on the results of PET/CT and histopathological analysis of the inguinal lymph node biopsy. After conducting a thorough diagnostic assessment, which included flow cytometry, next-generation sequencing (NGS), examination of immune-related gene rearrangements, and analysis of the immune repertoire of T-cell receptors (TCR), we conclusively determined that the hyperplastic T cells identified in the lymph node were the result of an expansion of CAR-T cells. Ultimately, the patient has attained complete remission (CR) and has sustained a disease-free survival state for 815 days as of the cutoff date on August 30, 2023. CONCLUSION: Taken together, the results demonstrate that anti-CD5 CAR-T cells can induce a clinical response in r/r ALK + ALCL patient. Furthermore, this case underscores the importance of utilizing advanced technologies with high sensitivity and accuracy for biological detection in clinical laboratory diagnosis and prognosis in CAR-T cell treatment. TRIAL REGISTRATION NUMBER: NCT04767308.
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