在一名晚期胆管癌患者中使用表皮生长因子受体（EGFR）特异性和CD133特异性嵌合抗原受体修饰的T细胞进行联合治疗。
Cocktail treatment with EGFR-specific and CD133-specific chimeric antigen receptor-modified T cells in a patient with advanced cholangiocarcinoma.
作者信息
Feng Kai-Chao, Guo Ye-Lei, Liu Yang, Dai Han-Ren, Wang Yao, Lv Hai-Yan, Huang Jian-Hua, Yang Qing-Ming, Han Wei-Dong
机构信息
Department of Bio-therapeutic, Institute of Basic Medicine, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, China.
Department of Immunology, Institute of Basic Medicine, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, China.
出版信息
J Hematol Oncol. 2017 Jan 5;10(1):4. doi: 10.1186/s13045-016-0378-7.
BACKGROUND
Cholangiocarcinoma (CCA) is one of the most fatal malignant tumors with increasing incidence, mortality, and insensitivity to traditional chemo-radiotherapy and targeted therapy. Chimeric antigen receptor-modified T cell (CART) immunotherapy represents a novel strategy for the management of many malignancies. However, the potential of CART therapy in treating advanced unresectable/metastatic CCA is uncharted so far.
CASE PRESENTATION
In this case, a 52-year-old female who was diagnosed as advanced unresectable/metastatic CCA and resistant to the following chemotherapy and radiotherapy was treated with CART cocktail immunotherapy, which was composed of successive infusions of CART cells targeting epidermal growth factor receptor (EGFR) and CD133, respectively. The patient finally achieved an 8.5-month partial response (PR) from the CART-EGFR therapy and a 4.5-month-lasting PR from the CART133 treatment. The CART-EGFR cells induced acute infusion-related toxicities such as mild chills, fever, fatigue, vomiting and muscle soreness, and a 9-day duration of delayed lower fever, accompanied by escalation of IL-6 and C reactive protein (CRP), acute increase of glutamic-pyruvic transaminase and glutamic-oxalacetic transaminase, and grade 2 lichen striatus-like skin pathological changes. The CART133 cells induced an intermittent upper abdominal dull pain, chills, fever, and rapidly deteriorative grade 3 systemic subcutaneous hemorrhages and congestive rashes together with serum cytokine release, which needed emergent medical intervention including intravenous methylprednisolone.
CONCLUSIONS
This case suggests that CART cocktail immunotherapy may be feasible for the treatment of CCA as well as other solid malignancies; however, the toxicities, especially the epidermal/endothelial damages, require a further investigation.
TRIAL REGISTRATION
ClinicalTrials.gov NCT01869166 and NCT02541370 .
背景
胆管癌（CCA）是最致命的恶性肿瘤之一，其发病率、死亡率不断上升，且对传统放化疗和靶向治疗不敏感。嵌合抗原受体修饰的T细胞（CART）免疫疗法是治疗多种恶性肿瘤的一种新策略。然而，CART疗法治疗晚期不可切除/转移性CCA的潜力目前尚不清楚。
病例介绍
在本病例中，一名52岁女性被诊断为晚期不可切除/转移性CCA，对后续化疗和放疗均耐药，接受了CART鸡尾酒免疫疗法治疗，该疗法由先后输注分别靶向表皮生长因子受体（EGFR）和CD133的CART细胞组成。患者最终从CART-EGFR治疗中获得了8.5个月的部分缓解（PR），从CART133治疗中获得了持续4.5个月的PR。CART-EGFR细胞诱导了急性输注相关毒性，如轻度寒战、发热、疲劳、呕吐和肌肉酸痛，以及持续9天的低热，伴有白细胞介素-6和C反应蛋白（CRP）升高、谷丙转氨酶和谷草转氨酶急性升高，以及2级线状苔藓样皮肤病理改变。CART133细胞诱导了间歇性上腹部隐痛、寒战、发热，以及迅速恶化的3级全身性皮下出血和充血性皮疹，同时伴有血清细胞因子释放，需要紧急医疗干预，包括静脉注射甲泼尼龙。
结论
本病例表明，CART鸡尾酒免疫疗法治疗CCA以及其他实体恶性肿瘤可能是可行的；然而，其毒性，尤其是表皮/内皮损伤，需要进一步研究。
试验注册
ClinicalTrials.gov NCT01869166和NCT02541370 。
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