Department of Personalized Cancer Immunotherapy, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
Cancer Center, Mie University Hospital, Tsu, Mie, Japan
BMJ Open. 2022 Nov 14;12(11):e065109. doi: 10.1136/bmjopen-2022-065109.
Adoptive cell transfer of genetically engineered T cells is a promising treatment for malignancies; however, there are few ideal cancer antigens expressed on the cell surface, and the development of chimeric antigen receptor T cells (CAR-T cells) for solid tumour treatment has been slow. CAR-T cells, which recognise major histocompatibility complex and peptide complexes presented on the cell surface, can be used to target not only cell surface antigens but also intracellular antigens. We have developed a CAR-T-cell product that recognises the complex of HLA-A*02:01 and an epitope of the MAGE-A4 antigen equipped with a novel signalling domain of human GITR (investigational product code: MU-MA402C) based on preclinical studies.
This is a dose-escalation, multi-institutional, phase 1 study to evaluate the tolerability and safety of MU-MA402C for patients with MAGE A4-positive and HLA-A*02:01-positive unresectable advanced or recurrent solid cancer. Two dose cohorts are planned: cohort 1, MU-MA402C 2×10/person; cohort 2, MU-MA402C 2×10/person. Prior to CAR-T-cell infusion, cyclophosphamide (CPA) and fludarabine (FLU) will be administered as preconditioning chemotherapy. Three evaluable subjects per cohort, for a total of 6 subjects (maximum of 12 subjects), will be recruited for this clinical trial. The primary endpoints are safety and tolerability. The severity of each adverse event will be evaluated in accordance with Common Terminology Criteria for Adverse Events V.5.0. The secondary endpoint is efficacy. Antitumour response will be evaluated according to Response Evaluation Criteria in Solid Tumours V.1.1.
This clinical trial will be conducted in accordance with the current version of Good Clinical Practice. The protocol was approved by the Clinical Research Ethics Review Committee of Mie University Hospital (approval number F-2021-017). The trial results will be published in peer-reviewed journals and/or disseminated through international conferences.
jRCT2043210077.
过继细胞转移基因工程 T 细胞是治疗恶性肿瘤的一种有前途的方法；然而，细胞表面表达的理想癌症抗原很少，实体瘤治疗嵌合抗原受体 T 细胞（CAR-T 细胞）的发展一直缓慢。CAR-T 细胞识别细胞表面呈现的主要组织相容性复合体和肽复合物，不仅可以靶向细胞表面抗原，还可以靶向细胞内抗原。我们基于临床前研究开发了一种 CAR-T 细胞产品，该产品识别 HLA-A*02:01 与 MAGE-A4 抗原表位的复合物，并配备了人类 GITR 的新型信号结构域（研究产品代码：MU-MA402C）。
这是一项剂量递增、多机构、I 期研究，旨在评估 MU-MA402C 在 HLA-A*02:01 阳性、无法切除的晚期或复发性实体癌的 MAGE A4 阳性患者中的耐受性和安全性。计划两个剂量队列：队列 1，MU-MA402C 2×10/人；队列 2，MU-MA402C 2×10/人。在 CAR-T 细胞输注前，将给予环磷酰胺（CPA）和氟达拉滨（FLU）作为预处理化疗。每个队列招募 3 名可评估受试者，总共 6 名受试者（最多 12 名受试者）将参加这项临床试验。主要终点是安全性和耐受性。根据不良事件通用术语标准 V.5.0 评估每个不良事件的严重程度。次要终点是疗效。根据实体瘤反应评价标准 V.1.1 评估抗肿瘤反应。
本临床试验将按照现行《良好临床实践》进行。该方案已获得三重大学医院临床研究伦理审查委员会的批准（批准号 F-2021-017）。试验结果将发表在同行评议的期刊上和/或通过国际会议传播。
jRCT2043210077。
