{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T18:26:52Z","timestamp":1773944812772,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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 \u00d7 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.<\/jats:p>","DOI":"10.3390\/cancers17182968","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T07:51:46Z","timestamp":1757577106000},"page":"2968","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["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"],"prefix":"10.3390","volume":"17","author":[{"given":"Simone","family":"Thomas","sequence":"first","affiliation":[{"name":"Department for Internal Medicine III, Hematology and Internal Oncology, University Hospital Regensburg, 93053 Regensburg, Germany"},{"name":"Leibniz Institute for Immunotherapy, 93053 Regensburg, Germany"},{"name":"Bavarian Center for Cancer Research (BZKF), 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4844-4087","authenticated-orcid":false,"given":"Martin","family":"Wermke","sequence":"additional","affiliation":[{"name":"National Center for Tumor Diseases, University Hospital Carl Gustav Carus TU Dresden, 01307 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8398-285X","authenticated-orcid":false,"given":"Vladan","family":"Vu\u010dini\u0107","sequence":"additional","affiliation":[{"name":"Department of Hematology, Cell Therapy and Hemostaseology, University Leipzig Medical Center, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Wagner-Drouet","sequence":"additional","affiliation":[{"name":"Department of Haematology and Medical Oncology, University Medical Center Mainz, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Mackensen","sequence":"additional","affiliation":[{"name":"Bavarian Center for Cancer Research (BZKF), 91054 Erlangen, Germany"},{"name":"Department of Internal Medicine 5, Hematology and Oncology, University Hospital Erlangen, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6565-3393","authenticated-orcid":false,"given":"Robert","family":"Zeiser","sequence":"additional","affiliation":[{"name":"Department of Medicine I, Hematology, Oncology and Stem-Cell Transplantation, University of Freiburg Medical Center, 79110 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gesine","family":"Bug","sequence":"additional","affiliation":[{"name":"Department of Medicine 2, University Hospital, Goethe University Frankfurt, 60596 Frankfurt, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1579-1509","authenticated-orcid":false,"given":"Michael","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Internal Medicine V, Hematology, Oncology and Rheumatology, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Herr","sequence":"additional","affiliation":[{"name":"Department for Internal Medicine III, Hematology and Internal Oncology, University Hospital Regensburg, 93053 Regensburg, Germany"},{"name":"Bavarian Center for Cancer Research (BZKF), 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra U.","family":"Prinz","sequence":"additional","affiliation":[{"name":"Medigene AG, 82152 Planegg-Martinsried, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1819-2122","authenticated-orcid":false,"given":"Maja","family":"B\u00fcrdek","sequence":"additional","affiliation":[{"name":"Medigene AG, 82152 Planegg-Martinsried, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silke","family":"Raffegerst","sequence":"additional","affiliation":[{"name":"Medigene AG, 82152 Planegg-Martinsried, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Tafuri","sequence":"additional","affiliation":[{"name":"Medigene AG, 82152 Planegg-Martinsried, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christiane","family":"Geiger","sequence":"additional","affiliation":[{"name":"Medigene AG, 82152 Planegg-Martinsried, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirsty","family":"Crame","sequence":"additional","affiliation":[{"name":"Medigene AG, 82152 Planegg-Martinsried, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ren\u00e9","family":"Goedkoop","sequence":"additional","affiliation":[{"name":"Medigene AG, 82152 Planegg-Martinsried, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Pinkernell","sequence":"additional","affiliation":[{"name":"Medigene AG, 82152 Planegg-Martinsried, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dolores J.","family":"Schendel","sequence":"additional","affiliation":[{"name":"Medigene AG, 82152 Planegg-Martinsried, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1182\/blood-2009-03-209387","article-title":"Dendritic cells pulsed with RNA encoding allogeneic MHC and antigen induce T cells with superior anti-tumor activity and higher TCR functional 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