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First-in-human study of MDG1011, a TCR-T therapy directed against HLA-A*02:01-Restricted PRAME antigen for high-risk myeloid and lymphoid neoplasms

Background/objectives: MDG1011 is a Preferentially Expressed Antigen in Melanoma (PRAME)-specific autologous T cell receptor (TCR) T cell therapy for HLA-A*02:01-positive patients. Data from the first-in-human (FIH) clinical trial, CD-TCR-001, are reported here regarding treatment feasibility, safet...

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Main Authors: Thomas, Simone (Author) , Wermke, Martin (Author) , Vučinić, Vladan (Author) , Wagner-Drouet, Eva (Author) , Mackensen, Andreas (Author) , Zeiser, Robert (Author) , Bug, Gesine (Author) , Schmitt, Michael (Author) , Herr, Wolfgang (Author) , Prinz, Petra U. (Author) , Bürdek, Maja (Author) , Raffegerst, Silke (Author) , Tafuri, Anna (Author) , Geiger, Christiane (Author) , Crame, Kirsty (Author) , Goedkoop, René (Author) , Pinkernell, Kai (Author) , Schendel, Dolores J. (Author)
Format: Article (Journal)
Language:English
Published: 2025
In: Cancers
Year: 2025, Volume: 17, Issue: 18, Pages: 1-18
ISSN:2072-6694
DOI:10.3390/cancers17182968
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.3390/cancers17182968
Verlag, kostenfrei, Volltext: https://www.mdpi.com/2072-6694/17/18/2968
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Author Notes:Simone Thomas, Martin Wermke, Vladan Vučinić, Eva Wagner-Drouet, Andreas Mackensen, Robert Zeiser, Gesine Bug, Michael Schmitt, Wolfgang Herr, Petra U. Prinz, Maja Bürdek, Silke Raffegerst, Anna Tafuri, Christiane Geiger, Kirsty Crame, René Goedkoop, Kai Pinkernell and Dolores J. Schendel
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Summary:Background/objectives: MDG1011 is a Preferentially Expressed Antigen in Melanoma (PRAME)-specific autologous T cell receptor (TCR) T cell therapy for HLA-A*02:01-positive patients. Data from the first-in-human (FIH) clinical trial, CD-TCR-001, are reported here regarding treatment feasibility, safety, tolerability, and clinical activity of MDG1011 in patients with relapsed/refractory (r/r) acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and multiple myeloma (MM). Methods: Nine of thirteen enrolled patients received MDG1011 at dose levels ranging from 0.1 to 5 × 106 TCR-T cells per kg body weight. In addition to clinical assessments, immune monitoring of cytokines associated with cytokine release syndrome (CRS), presence and persistence of MDG1011, and changes in levels of PRAME mRNA were used to assess safety and potential biological activity at defined time points. Results: The treatment was well tolerated. No dose-limiting toxicities (DLTs) were observed, and the most common serious adverse events were associated with lymphodepleting chemotherapy and/or disease progression. Various parameters, such as measurable clinical responses in two patients, the occurrence of CRS in two additional patients, and reductions in PRAME mRNA levels in bone marrow (BM) or peripheral blood (PB) in seven patients, served as signs of the clinical and biological activity of MDG1011 TCR-T therapy. Conclusions: Patients enrolled in the phase 1 part of CD-TCR-001 displayed signs of potential clinical and biological activity of MDG1011 among the small number of patients studied. Advanced disease stage and rapid progression in the r/r AML patients limited clinical impact. The acceptable safety profile of MDG1011 merits further investigation of this TCR-T therapy, potentially in patients at an earlier stage of their disease and with lower tumor burden.
Item Description:Online veröffentlicht am 11. September 2025
Gesehen am 16.04.2026
Physical Description:Online Resource
ISSN:2072-6694
DOI:10.3390/cancers17182968

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