Anton Martens

Principle Investigator

Biographical Sketch

Anton Martens (1952) studied Clinical Chemistry at the BMAS-HLO, Breda, The Netherlands from 1968-1971. In 1988 he obtained his PhD from the University of Leiden, The Netherlands. Research for his thesis on “Normal and leukemic stem cells during minimal residual disease”, was conducted at the Radiobiological Institute TNO under guidance of Prof D.W. van Bekkum.

In 1993 he moved to the Department of Hematology, Erasmus University Rotterdam, The Netherlands (head Prof. B. Löwenberg) were he conducted research on experimental therapy for treatment of acute leukemia in animal models.

In 1997 he moved to the Department of Hematology, University Medical Center Utrecht were he continued stem cell oriented research in Hemato-oncology. At the UMC Utrecht he implemented bioluminescence imaging (BLI) technology as a tool for in vivo monitoring of normal and leukemic stem cells and various other applications in preclinical biomedical research. His research interest shifted towards the development of experimental therapies for Multiple Myeloma.
In 2007 he joined the department of Immunology (Head. Prof. Frank Miedema) were he continued his research on characterization of mesenchymal stem cells in bone development and used this to establish a novel fully humanized mouse model to study the pathogenesis of human multiple myeloma (MM) in its natural environment and to use the model to monitor tumor growth and response of chemotherapy and immunotherapy using imaging technology.

From 2011 he is continuing this research at the Department of Cell Biology (Head. Prof. Judith Klumperman).

Key Publications

Rozemuller H, Prins H-J, Naaijkens B, Staal J, Bühring H-J and Martens AC. Prospective isolation of mesenchymal stem cells from multiple mammalian species using cross-reacting anti human monoclonal antibodies. Stem Cells Dev, Stem Cells Dev. 2010 Dec;19(12):1911-21. Epub 2010 Aug 12

van Meerten T, Rozemuller H, Hol S, Moerer P, Zwart M, Hagenbeek A, Mackus JWM, Parren PWHI, van de Winkel JGJ, Ebeling SB and Martens A. Rituximab-resistance of CD20low cells can be overcome by HuMab-7D8, a monoclonal antibody directed against the membrane-proximal small loop epitope of CD20. Haematologica 2010 vol. 95 (12) pp. 2063-71

Spaapen RM, Groen RWJ ,van den Oudenalder K, , Guichelaar T, van Elk M, Aarts T, Bloem AC, Storm G, Martens AC, Lokhorst HM and Mutis T Induction of Potent in Vivo Anti-tumor Effects by Native and TCR- Guichelaar T, Rozemuller H, Emmelot M, Aarts T, Storm G, Lokhorst H, Martens AC and Mutis T. The in vivo impact of ex vivo cultured Human Regulatory T cells on the Graft-versus-Tumor effect in Multiple Myeloma. Clin Cancer Res (2010) vol. 16 (22) pp. 5481-7

Reijmers RM, Groen RJW, Rozemuller H, Kuil A, de Haan-Kramer A,Csikós T, Martens AC, Spaargaren M and T. Pals S. Targeting EXT-1 reveals a crucial role for heparan sulfate in the growth of multiple myeloma. Blood 2010 vol. 115 (3) pp. 601-604

Rozemuller H, van der Spek E, Bogers-Boer LH, Zwart MC, Verweij V, Emmelot ME, Groen RW Spaapen R, Bloem AC, Lokhorst HM, Mutis T, Martens AC A bioluminescence imaging based in vivo model for preclinical testing of novel cellular immunotherapy strategies to improve Graft versus Myeloma Hematologica 2008 Jul;93(7):1049-57 Epub 2008 May 19. PubMed PMID: 18492693.

Prins HJ, Rozemuller H, Vonk-Griffioen S, Verweij VG, Dhert W, Slaper-Cortenbach I, Martens AC. Bone Forming Capacity of Mesenchymal Stromal Cells when Cultured in the Presence of Human Platelet Lysate as Substitute for Fetal Bovine Serum. Tissue Eng Part A. 2009 Dec;15(12):3741-51

Postnov AA, Rozemuller H, Verwey V, Lokhorst H, De Clerck N, Martens AC. Correlation of High-Resolution X-Ray Micro-Computed Tomography with Bioluminescence Imaging of Multiple Myeloma Growth in a Xenograft Mouse Model Calcif Tissue Int. 2009 November; 85(5): 434–443

Olivo C, Alblas J, Verweij V, Van Zonneveld AJ, Dhert WJ, Martens AC. In vivo bioluminescence imaging study to monitor ectopic bone formation by luciferase gene marked mesenchymal stem cells. J Orthop Res. 2008 Jul;26(7):901-9. PubMed PMID: 18271011

Rozemuller H, Knaän-Shanzer S, Hagenbeek A, van Bloois L, Storm G, , and Martens ACM. Enhanced Engraftment Of Human Cells In RAG2/gc Double Knock out Mice After Treatment With CL2MDP-Liposomes Exp Hemat 32 (2004) pp. 1118-1125.

Kruyt MC, Stijns MMC, Fedorovich NE, de Bruijn JD, van Blitterswijk CA, Verbout AJ, Rozemuller H, Hagenbeek A, Dhert WJA and Martens ACM. Genetic marking with the dLNGFR-gene for tacing goat cells in bone tissue engineering. Journal of Orthopaedic Research 22 (2004) pp. 697-702.

van Rijn RS, Simonetti ER, Hagenbeek A, Hogenes MC, de Weger RA, Canninga-van Dijk MR, Weijer K, Spits H, Storm G, van Bloois L, Rijkers G, Martens AC, Ebeling SB. A new xenograft model for graft-versus-host disease by intravenous transfer of human peripheral blood mononuclear cells in RAG2-/- gammac-/- double-mutant mice. Blood. 2003 Oct 1;102(7):2522-31. Epub 2003 Jun

Rombouts WJC, Martens ACM and Ploemacher RE. Identification of variables determining the engraftment potential of human acute myeloid leukemia in the immunodeficient NOD/SCID human chimera model. Leukemia, 14 (5): 889-97 (2000).

Rozemuller H, Rombouts WJC, Touw IP, FitzGerald DJP, Kreitman RJ, Hagenbeek A, Martens ACM (1998) In vivo targeting of leukemic cells using diphtheria toxin fused to murine GM-CSF. Leukemia 12; 710-717 (1999)

Terpstra W, Rozemuller H, Breems DA, Rombouts WJC, Prins A, FitzGerald DJP, Kreitman RJ, Wielenga JJ, Ploemacher RE, Löwenberg B, Hagenbeek A, Martens ACM Diphtheria toxin fused to GM-CSF eliminates AML cells with the potential to initiate leukemia in immunodeficient mice, but spares normal hemopoietic stem cells. Blood 90; 3735-3742 (1997)

Rozemuller H, Terpstra W, Rombouts WJC, Lawler M, Byrne C, FitzGerald DJP, Kreitman RJ, Wielenga JJ, Löwenberg B, Touw IP, Hagenbeek A, Martens ACM (1998) GM-CSF receptor targeted treatment of primary AML in SCID mice using Diphtheria toxin fused to huGM-CSF. Leukemia 12; 1962-1970 (1998).

Grants obtained

Dutch Cancer Society (KWF-NKB)
Characterization of cytogenetically undefined marker chromosomes in human leukemia using flow sorting, PCR and "reverse painting" in situ hybridization. 1993-1997*
A. Hagenbeek and ACM Martens

Dutch Cancer Society (KWF-NKB)
Cytokine gene mediated immunotherapy of leukemia. 1993-1997
A. Hagenbeek and ACM Martens

Dutch Cancer Society (KWF-NKB)
Growth factor-toxin fusion proteins targeted to hemopoietic growth factor receptors for the treatment of acute leukemia. 1994-1997
ACM Martens and I.P. Touw

Dutch Cancer Society (KWF-NKB)
Immunotherapy of minimal residual leukemia with suicide gene transduced cells.
A. Hagenbeek, ACM Martens

Dutch Cancer Society (KWF-NKB)
Growth factor toxins for treatment of acute myelocytic leukemia
ACM Martens and I. Touw 1994-1998

ZonMW/NOW 2003
Photon detection camera for real time non-invasive imaging
ACM Martens, S. Ebeling

Association for International Cancer Research (AICR) UK 2007-2010
The Impact of Regulatory T Cells on The Graft vs Tumor Effect
T. Mutis, ACM Martens, H. Lokhorst

Wilhelmina Children's Hospital Foundation (WKZ Fonds)
Stem cell based therapy for Hurler’s Disease 2006-2009
N. Wulfraat, ACM Martens

Netherlands Scientific Organisation (Zon-MW)
Gene therapy for lysosomal storage diseases.
G. Wagemaker, N. Wulffraat, ACM Martens 2008-2011

Dutch Program for Tissue Engineering (NWO-DPTE) 2006-2011
Non-invasive bioluminescence imaging in animal models for stem cell transplantation, bone tissue engineering and osteoporosis
ACM Martens

Vanderes Foundation 2009-2011
Development of humanized mouse model to study engraftement of leukemic and normal stem cells
ACM Martens

Biotech sponsored research
Therapeutic efficacy of huMax-CD38 for treatment of human myeloma 2008-2013
ACM Martens

Multiple Myeloma Research Foundation 2010
A humanized mouse model to study multiple myeloma
ACM Martens

Research interest