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Updated: Aug 22, 2025
A Real-time Potency Assay for Chimeric Antigen Receptor T Cells Targeting Solid and Hematological Cancer Cells
Published on: November 12, 2019
Chimeric antigen receptor T-cell therapy targeting a MAGE A4 peptide and HLA-A*02:01 complex for unresectable
Satoshi Okumura1, Mikiya Ishihara2, Naomi Kiyota3,4
1Department of Personalized Cancer Immunotherapy, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
Introduction:
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.
Methods And Analysis:
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 2×108/person; cohort 2, MU-MA402C 2×109/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.
Ethics And Dissemination:
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.
Trial Registration Number:
jRCT2043210077.
Insights
This Phase 1 clinical trial evaluates MU-MA402C, a novel chimeric antigen receptor T-cell (CAR-T) therapy targeting MAGE-A4 and HLA-A*02:01 in solid tumors. The study assesses safety and tolerability of this advanced cancer treatment.
Area of Science:
- Oncology
- Immunotherapy
- Cellular Therapy
Background:
- Adoptive cell transfer using genetically engineered T cells shows promise for malignancies.
- Chimeric antigen receptor T cells (CAR-T) development for solid tumors is challenging due to limited surface antigens.
- CAR-T cells can target intracellular antigens by recognizing MHC-peptide complexes.
Purpose of the Study:
- To evaluate the tolerability and safety of MU-MA402C in patients with MAGE A4-positive and HLA-A*02:01-positive unresectable advanced or recurrent solid cancer.
- To assess the efficacy of MU-MA402C as a novel cancer immunotherapy.
Main Methods:
- A dose-escalation, multi-institutional Phase 1 clinical trial.
- Two dose cohorts of MU-MA402C (2x10^8/person and 2x10^9/person) will be administered.
- Preconditioning chemotherapy with cyclophosphamide (CPA) and fludarabine (FLU) will be given prior to CAR-T infusion.
Main Results:
- Primary endpoints are safety and tolerability, assessed using Common Terminology Criteria for Adverse Events V.5.0.
- Secondary endpoint is efficacy, evaluated by antitumour response using Response Evaluation Criteria in Solid Tumours V.1.1.
- The study will recruit up to 12 subjects.
Conclusions:
- MU-MA402C represents a novel CAR-T cell product targeting the HLA-A*02:01 and MAGE-A4 complex.
- This study will provide crucial safety and preliminary efficacy data for this innovative solid tumor treatment.
- Results will be disseminated through peer-reviewed publications and conferences.
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