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病例报告:B7-H3 CAR-T 治疗部分控制一例基底细胞癌患者的肿瘤生长

英文原题:Case report: B7-H3 CAR-T therapy partially controls tumor growth in a basal cell carcinoma patient.

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Case report: B7-H3 CAR-T therapy partially controls tumor growth in a basal cell carcinoma patient.

PubMed 2022/08/17(内容时间) Front Oncol Q2 · IF 3.4(JCR 2025)

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中文摘要

B7-H3在多种实体瘤中过表达,使其成为嵌合抗原受体(CAR)-T治疗的理想靶点。在此,我们首次报告一例多发性基底细胞癌(BCC)患者通过直接瘤内注射人源化单克隆抗B7-H3 CAR-T 细胞进行治疗。经过三次剂量递增注射后,腹部病灶体积缩小40%,从隆起变为平坦,但未完全消除。前额的大病灶从原来的溃疡和出血变为干燥。观察到的不良事件为瘙痒、肌痛和发红。免疫组化分析表明,注射CAR-T 细胞后,B7-H3阳性肿瘤细胞和B7-H3表达强度均降低。浸润性CD3 T细胞数量显著增加,但主要位于肿瘤区域外。随后,在肿瘤区域观察到高水平的TGF-,提示实体瘤微环境可能阻碍CAR-T 细胞的浸润和效应。

总之,在本特定病例报告中,瘤内注射B7-H3 CAR-T 细胞部分控制了BCC患者的肿瘤生长,且不良事件轻微。B7-H3 CAR-T 治疗的疗效和安全性需要在更大规模的患者队列中进一步研究。尽管此处仅报告一例临床病例,但抗B7-H3 CAR-T 细胞治疗应被视为未来实体瘤的一种治疗选择。该临床试验已在中国临床试验注册中心(www.chictr.org.cn)注册,注册号为ChiCTR2100044386。

展开英文摘要原文

B7-H3 is over-expressed in multiple types of solid tumors, making it an ideal target for chimeric antigen receptor (CAR)-T therapy.

Here, we first report a case of multiple basal cell carcinoma (BCC) patient treated with humanized monoclonal anti-B7-H3 CAR-T cells through direct intratumoral injection. After three dose-escalated injections, the lesion in the abdomen decreased by 40% in volume, shrank from bulging to flat, but was not eradicated completely. The large lesion in the forehead became dry from original ulcer and bleeding. The adverse events observed were itching, myalgia, and redness. Immunohistochemistry analysis demonstrated that B7-H3-positive tumor cells and B7-H3 expression intensity were reduced after injections of CAR-T cells. The number of infiltrating CD3 T cells increased significantly but mainly located outside the tumor region.

Subsequently, high levels of TGF- in the tumor area were observed, suggesting that solid tumor microenvironment may hinder the infiltration and effect of CAR-T cells. In summary, in this particular case report, intratumoral injection of B7-H3 CAR-T cells partially controls tumor growth in the BCC patient with minor adverse events.

The efficacy and safety of B7-H3 CAR-T therapy need to be further investigated with a larger cohort of patients. Although only one clinical case is reported here, the anti-B7-H3 CAR-T cell therapy should be considered as a treatment option for solid tumors in the future. This clinical trial was registered at the Chinese Clinical Trial Registry (www. chictr. org. cn) with registration number ChiCTR2100044386.

论文信息

作者
Hu G、Li G、Wen W、Ding W、Zhou Z、Zheng Y、Huang T、Ren J
第一作者单位
Department of Dermatology, Dermatology Hospital, Southern Medical University, Guangzhou, China.China
通讯作者单位
Research and Development Department Guangzhou Bio-Gene Technology Co., Ltd., Guangzhou, China.China
文献类型
病例报告
期刊
Frontiers in oncology2022
原文标识
PubMed 36059640 · DOI 10.3389/fonc.2022.956593