GDF-15 - a key modulator of
antitumoral immune responses
Growth Differentiation Factor-15 (GDF-15) is a remote member of the multifunctional transforming growth factor β cytokine superfamily. This cytokine is associated with a poor clinical outcome for cancer patients and reduced overall survival in various cancer indications. Tumors express and release high amounts of GDF-15 in its microenvironment, which allows them to avoid recognition by the circulating immune cells and mount an antitumoral immune response.


GDF-15 acts via the following mechanisms:
- interfering with DC activation and maturation
- reducing T-cell priming and activation by dendritic cells
- blocking the effective immune cell extravasation and tumor infiltration
- inhibiting T-cell and NK-cell-based killing of tumor cells
- inducing immunosuppression in the tumor tissue by generation and
function enhancement of regulatory T-cells
Catalym Corporate Video
How we neutralize GDF-15 within the tumor microenvironment
Click to see the movie.
Neutralization of GDF-15
as a therapeutic concept to reverse tumor-mediated immunosuppression
GDF-15 is an important tool for tumors to build up resistance against checkpoint inhibitor therapy.
By neutralizing GDF-15, CatalYm aims to reverse this tumor-derived immunosuppression and make tumors accessible and susceptible again to the patient’s own immune system. Our preclinical and Phase 1 findings demonstrated that neutralizing GDF-15 can restore the ability of T cells to enter the tumor and could therefore improve responses to antitumoral therapies.
To find out how our therapeutic candidate can neutralize GDF-15 to expand the treatment horizon for immunotherapy-refractory cancer patients, check out the mechanism of action video above.

Our Scientific &
Clinical Advisors
On our path to expand the horizon of current immunotherapies, we are supported by an international team of seasoned experts in the immuno-oncology field.
Alexander Eggermont
MD, PhDProfessor Alexander Eggermont is General Director of Gustave Roussy Cancer Institute, Professor of Oncology at the Paris-Sud University, and Professor of Oncological Surgery at the Erasmus University of Rotterdam in Holland. He also holds the Honorary Joseph Maisin Honorary Chair of Oncological Surgery at the Louvain Catholic University in Belgium, and an Honorary Doctorate at the University of Essen-Duisburg, Germany. In addition, he serves as the President of the European Academy of Cancer Sciences, and the President of the Cancer Core Europe consortium. In 2015, Prof. Eggermont was elevated to the status of Chevalier of the Légion d’Honneur by the French Ministry of Foreign Affairs and International Development. His research specialty is in immunotherapy, the treatment of melanomas and sarcomas in addition to fundamental research in pathogenesis and immunology of tumors.
Professor Alexander Eggermont is General Director of Gustave Roussy Cancer Institute, Professor of Oncology at the Paris-Sud University, and Professor of Oncological Surgery at the Erasmus University of Rotterdam in Holland. He also holds the Honorary Joseph Maisin Honorary Chair of Oncological Surgery (...)
Ignacio Melero
MD, PhDProfessor Melero is Professor of Immunology at the Clinic of the University of Navarra and at the Center for Applied Medical Research of the University of Navarra, Pamplona, Spain. His current areas of research are focused on translational research with cell, gene and monoclonal antibody-mediated strategies for cancer immunotherapies. Dr. Melero has been awarded the BIAL Prize of Medicine, the Conde de Cartagena Award from the Royal Academy of Medicine, Doctor Durantez LAIR Foundation Award and a Cancer Research Institute research award. He has served on the advisory boards of Bristol Myers-Squibb, Roche-Genentech, AstraZeneca, Merck Serono and Boehringer Ingelheim.
Professor Melero is Professor of Immunology at the Clinic of the University of Navarra and at the Center for Applied Medical Research of the University of Navarra, Pamplona, Spain. His current areas of research are focused on translational research with cell, gene and monoclonal antibody-mediated (...)
Jörg Wischhusen
PhDProfessor Wischhusen is scientific co-founder of CatalYm. He is also the Head of the Section of Experimental Tumor Immunology at the University of Würzburg Medical School, Germany. Prof. Wischhusen’s current research is directed towards tumor-host interactions in ovarian and breast cancer, with a strong focus on tumor-initiating cells and their ability to evade immunosurveillance. Previously, he was a research group leader at the Interdisciplinary Center for Clinical Research in Würzburg. He received his PhD from the University of Tübingen, Germany in the field of molecular neuro-oncology.
Professor Wischhusen is scientific co-founder of CatalYm. He is also the Head of the Section of Experimental Tumor Immunology at the University of Würzburg Medical School, Germany. Prof. Wischhusen’s current research is directed towards tumor-host interactions in ovarian and breast cancer, with (...)
Ralf C. Bargou
MD, PhDProfessor Ralf C. Bargou is Director of the Mainfranken Comprehensive Cancer Center and Chair of the Translational Oncology Department at Würzburg University. He also serves as member of the Board of Directors of the newly formed Bavarian Cancer Research Center. He has a long-standing and successful track record for development of innovative immunotherapies for cancer and was instrumental for the preclinical, translational and clinical development of Blincyto™. Prof. Bargou’s prime research interests are tumor immunology and cancer immunotherapy. He is author of over 130 scientific publications and has been awarded the Paul-Martini prize for outstanding pharmacological research in 2009 and the Inventor of the Year award in 2016 of the Intellectual Property Owners Education Foundation in Washington D.C..
Professor Ralf C. Bargou is Director of the Mainfranken Comprehensive Cancer Center and Chair of the Translational Oncology Department at Würzburg University. He also serves as member of the Board of Directors of the newly formed Bavarian Cancer Research Center. He has a long-standing and successful (...)
Reinhard Dummer
MDProfessor Reinhard Dummer is Professor of the University of Zürich and Vice-Chairman of the Department of Dermatology in the University Hospital of Zürich, Switzerland and is a key thought leader in worldwide cutaneous oncology. Currently, he is heading the Skin Cancer Unit and the Clinical Trial Unit of the Department of Dermatology. Prof. Dummer’s principal research interests are molecular biology, immunology and immunotherapy of cutaneous malignancies, including cutaneous lymphomas and melanomas and has published more than 741 scientific publications. He is a founding and Board Member of the European Association of Dermato-Oncology, ESMO, URPP and a member of the German National Academy of Sciences (Leopoldina). Prof. Dummer began his medical education in hematology and oncology before successfully completing his dermatology residency in Würzburg, Germany, and Zürich, Switzerland.
Professor Reinhard Dummer is Professor of the University of Zürich and Vice-Chairman of the Department of Dermatology in the University Hospital of Zürich, Switzerland and is a key thought leader in worldwide cutaneous oncology. Currently, he is heading the Skin Cancer Unit and the Clinical Trial (...)
Stephen Hodi
MDDr. F. Stephen Hodi is the Director of the Melanoma Center and the Center for Immuno-Oncology at Dana-Farber / Brigham and Women’s Cancer Center, the Sharon Crowley Martin Chair in Melanoma at Dana- Farber Cancer Institute and Professor of Medicine at Harvard Medical School. His internationally recognized research focuses on gene therapy, the development of immune therapies, and first into human studies for malignant melanoma. Dr. Hodi is a member of ASCO, AACR, the ECOG Melanoma Committee, SITC, the European Academy of Tumor Immunology and a founding member of the Society for Melanoma Research. His clinical investigation efforts have pioneered the use of immune checkpoint blockade and combinatorial approaches to treat cancer. He has published over 300 peer-reviewed scientific publications including articles in the Proceedings of the National Academy of Sciences, Journal of Clinical Oncology and the New England Journal of Medicine.
Dr. F. Stephen Hodi is the Director of the Melanoma Center and the Center for Immuno-Oncology at Dana-Farber / Brigham and Women’s Cancer Center, the Sharon Crowley Martin Chair in Melanoma at Dana- Farber Cancer Institute and Professor of Medicine at Harvard Medical School. His internationally (...)
Thomas Gajewski
MD, PhDProfessor Thomas Gajewski is Professor in the Departments of Pathology and Medicine at the University of Chicago. He oversees the melanoma oncology clinic and is the leader of the Immunology and Cancer Program at the University of Chicago Comprehensive Cancer Center. Prof. Gajewski is committed to investigating and developing new treatments for patients with melanoma, with a special interest in the development of immunotherapies, and is an author/co-author of over 270 scientific publications in the field. He serves as an editor for Cancer Discovery, Journal for Experimental Medicine, and the Journal for Immunotherapy of Cancer, is on the Program Committees for the American Society for Clinical Oncology (ASCO) and the American Association for Cancer Research (AACR), and is past President of the Society for Immunotherapy of Cancer.
Professor Thomas Gajewski is Professor in the Departments of Pathology and Medicine at the University of Chicago. He oversees the melanoma oncology clinic and is the leader of the Immunology and Cancer Program at the University of Chicago Comprehensive Cancer Center. Prof. Gajewski is committed (...)
Wolf H. Fridman
MD, PhDProfessor Wolf H. Fridman is Professor Emeritus of Immunology at the Paris Descartes University Medical School in Paris, France. He received his MD and PhD degrees from the University of Paris. He has been the founder and first Director of the Cordeliers Research Centre, a joint research structure between INSERM, University Paris Descartes, and University Pierre et Marie Curie.
He was also the Head of the Immunology Laboratory of European Hospital Georges Pompidou in Paris. Prof. Fridman’s current research is focused on the immune response in the tumor microenvironment to control clinical outcomes in cervical cancer. He is a world leader in the field of human tumor immunology and has authored over 480 scientific publications in the field.
Professor Wolf H. Fridman is Professor Emeritus of Immunology at the Paris Descartes University Medical School in Paris, France. He received his MD and PhD degrees from the University of Paris. He has been the founder and first Director of the Cordeliers Research Centre, a joint research structure (...)
Publications
Scientific validation for GDF-15 as a central key player in the immune resistance of cancer
list of publications, including link to each paper
Tumor-derived GDF-15 prevents therapy success of checkpoint inhibitors by blocking T-lymphocyte recruitment
Markus Haake, Tina Schäfer, Beatrice Haack, Neha Vashist, Sabrina Genßler, Patrick Harter, Alexander Martens, Kilian Wistuba-Hamprecht, Florian Wedekink, Birgitt Fischer, Michel Mittelbronn, Mitchell Levesque, Phil Cheng, Reinhard Dummer, Benjamin Weide, Kathrin Klar, Eugen Leo, Falk Nimmerjahn, Christine Schuberth-Wagner and Jörg Wischhusen J Immunother Cancer 2021;9(Suppl 2):A597
A phase I, first-in-human clinical trial of the GDF-15 neutralizing antibody CTL-002 in subjects with advanced stage solid tumors (Acronym: GDFATHER)
Ignacio Melero, Emiliano Calvo, Maria-Elisabeth Goebeler, Elena Garralda, Reinhard Dummer, María Rodríguez-Ruiz, Maria de Miguel, Cyrus Michael Sayehli, Guzman Alonso Casal, Egle Ramelyte, Martin Schuler, Tanja Gromke, Miguel Sanmamed, Irene Moreno, Ralf Bargou, Maria Lostes, Julia-Tatjana Maul, Corinne Eggenschwiler, Heike Richly, Petra Fettes, Kathrin Klar, Christine Schuberth-Wagner, Markus Haake, Jörg Wischhusen and Eugen Leo J Immunother Cancer 2021;9(Suppl 2):A536
Tumor-derived GDF-15 to suppress T-lymphocyte recruitment to the tumor microenvironment resulting in resistance to ANTI-PD-1 treatment.
Joerg Wischhusen, Markus Haake, Neha Vashist, Sabrina Genßler, Kilian Wistuba-Hamprecht, Patrick Harter, Alexander Martens, Michel Mittelbronn, Mitchell P. Levesque, Reinhard Dummer, Benjamin Weide, Marij JP Welters, Sjoerd H van der Burg, Manfred Ruediger, Eugen Leo, Falk Nimmerjahn, and Christine Schuberth-Wagner Journal of Clinical Oncology 2021 39:15_suppl, e14532-e14532
Colchicine acts selectively in the liver to induce hepatokines that inhibit myeloid cell activation
Jui-Hsia Weng, Peter David Koch, Harding H. Luan, Ho-Chou Tu, Kenichi Shimada, Iris Ngan, Richard Ventura, Ruomu Jiang and Timothy J. Mitchison Nat Metab 3, 513–522 (2021).
GDF15 induces immunosuppression via CD48 on regulatory T cells in hepatocellular carcinoma
Zhaowei Wang, Lei He, Weina Li, Chuanyang Xu, Jieyu Zhang, Desheng Wang, Kefeng Dou, Ran Zhuang, Boquan Jin, Wei Zhang, Qiang Hao, Kuo Zhang, Wangqian Zhang, Shuning Wang, Yuan Gao, Jintao Gu, Lei Shang, Zhijun Tan, Haichuan Su, Yingqi Zhang, Cun Zhang, Meng Li Immunother Cancer. 2021 Sep;9(9):e002787. doi: 10.1136/jitc-2021-002787. PMID: 34489334.
Tumor-derived GDF-15 suppresses T-lymphocyte recruitment to the tumor microenvironment
Markus Haake, Neha Vashist, Sabrina Genssler, Kristin H. Eichler, Birgitt Fischer, Jessica Kammer, Paula S. Romer, Manfred Rudiger, Eugen Leo, Falk Nimmerjahn, Christine Schuberth-Wagner and Joerg Wischhusen Cancer Res August 15 2020 (80) (16 Supplement) 5597; DOI: 10.1158/1538-7445.AM2020-5597
Growth/Differentiation Factor-15 (GDF-15): From Biomarker to Novel Targetable Immune Checkpoint
Joerg Wischhusen J, Ignacio Melero,Wolf Herman Fridman Front Immunol. 2020 May 19;11:951. doi: 10.3389/fimmu.2020.00951. PMID: 32508832; PMCID: PMC7248355.
Circulating growth/differentiation factor 15 is associated with human CD56bright natural killer cell dysfunction and nosocomial infection in severe systemic inflammation
Holger Kleinertz, Monika Hepner-Schefczyk, Sabrina Ehnert, Maren Claus, Rebecca Halbgebauer, Lea Boller, Markus Huber-Lang, Paolo Cinelli, Carsten Kirschning, Sascha Flohé, André Sander, Christian Waydhas, Sonja Vonderhagen, Marcus Jäger, Marcel Dudda, Carsten Watzl, Stefanie B. Flohé EBioMedicine. 2019 May;43:380-391. doi: 10.1016/j.ebiom.2019.04.018. PMID: 30992245; PMCID: PMC6557805.
High GDF-15 Serum Levels Independently Correlate with Poorer Overall Survival of Patients with Tumor-Free Stage III and Unresectable Stage IV Melanoma
BenjaminWeide, Tina Schäfer, Alexander Martens, Anastasia Kuzkina, Laura Uder, Seema Noor, Claus Garbe, Patrick N. Harter, Michel Mittelbronn and Jörg Wischhusen J Invest Dermatol. 2016 Dec;136(12):2444-2452. doi: 10.1016/j.jid.2016.07.016. PMID: 27705749.
GDF-15 is an inhibitor of leukocyte integrin activation required for survival after myocardial infarction in mice
Tibor Kempf, Alexander Zarbock, Christian Widera, Stefan Butz, Anika Stadtmann, Jan Rossaint , Matteo Bolomini-Vittori, Mortimer Korf-Klingebiel, L Christian Napp, Birte Hansen, Anna Kanwischer, Udo Bavendiek, Gernot Beutel, Martin Hapke, Martin G Sauer, Carlo Laudanna, Nancy Hogg, Dietmar Vestweber & Kai C Wollert. Nat Med. 2011 May;17(5):581-8. doi: 10.1038/nm.2354. PMID: 21516086.
GDF-15 contributes to proliferation and immune escape of malignant gliomas
P. Roth, M. Junker, I. Tritschler, M. Mittelbronn, Y. Dombrowski, S. N. Breit, G. Tabatabai, W. Wick, M. Weller, J. Wischhusen, Clin Cancer Res 16, 3851-3859 (2010)
MIC-1 serum level and genotype: associations with progress and prognosis of colorectal carcinoma
D. A. Brown, R. L. Ward, P. Buckhaults, T. Liu, K. E. Romans, N. J. Hawkins, A. R. Bauskin, K. W. Kinzler, B. Vogelstein, S. N. Breit, Clin Cancer Res 9, 2642-2650 (2003)
MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily
M. R. Bootcov, A. R. Bauskin, S. M. Valenzuela, A. G. Moore, M. Bansal, X. Y. He, H. P. Zhang, M. Donnellan, S. Mahler, K. Pryor, B. J. Walsh, R. C. Nicholson, W. D. Fairlie, S. B. Por, J. M. Robbins, S. N. Breit, Proc Natl Acad Sci U S A 94, 11514-11519 (1997).