Tom van Meerten
dr.
I am a hematologist involved in patient care, clinical and translation research in the field of malignant lymphoma. I focus on translational medicine on diffuse large B cell lymphoma and mantle cell lymphoma. My question by all our findings: how does the patient profit or does it help me to treat the patients. The focus of my research group is on DNA repair, cell cycle and cell death. We test novel combinations of existing anti-cancer agents to ultimately improve the treatment of patients suffering from lymphoma. I participate in the organization of new clinical trials both international (European Mantle cell Lymphoma Network) and national (HOVON). Moreover, I am actively involved in clinical trials concerning the application of CAR T cells for patient with lymphoma.
Identification of relevant drugable targets in diffuse large B-cell lymphoma using a genome-wide unbiased CD20 guilt-by association approach
Published in: PLoS ONE
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10.1371/journal.pone.0193098
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Forty percent of patients with diffuse large B-cell lymphoma (DLBCL) show resistant disease to standard chemotherapy (CHOP) in combination with the anti-CD20 monoclonal antibody rituximab (R). Although many new anti-cancer drugs were developed in the last years, it is unclear which of these drugs can be safely combined to improve standard therapy without antagonizing anti-CD20 efficacy. In this study, we aimed to identify rituximab compatible drug-target combinations for DLBCL. For this, we collected gene expression profiles of 1,804 DLBCL patient samples. Subsequently, we performed a guilt-by-association analysis with...
Mathilde R. W. de Jong, Lydia Visser, Gerwin Huls, Arjan Diepstra, Marcel van Vugt, Emanuele Ammatuna, Rozemarijn S. van Rijn, Edo Vellenga, Anke van den Berg, Rudolf S. N. Fehrmann, Tom van Meerten
Performance of advanced imaging modalities at diagnosis and treatment response evaluation of patients with post-transplant lymphoproliferative disorder: A systematic review
Filipe Montes de Jesus, Thomas Kwee, Marcel Nijland, Xaver-Ulrich Kahle, Geert Huls, Rudi Dierckx, Tom van Meerten, Olivier Gheysens, D Dierickx, Walter Noordzij, Andor W.J.M. Glaudemans
CD20-selective inhibition of CD47-SIRP alpha “don’t eat me” signaling with a bispecific antibody-derivative enhances the anticancer activity of daratumumab, alemtuzumab and obinutuzumab
Published in: OncoImmunology
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10.1080/2162402X.2017.1386361
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Here, we report on a novel bispecific antibody-derivative, designated RTX-CD47, with unique capacity for CD20-directed inhibition of CD47-SIRP alpha “don’t eat me” signaling. RTX-CD47 comprises a CD20-targeting scFv antibody fragment derived from rituximab fused in tandem to a CD47-blocking scFv. Single agent treatment with RTX-CD47 triggered significant phagocytic removal of CD20(pos)/CD47(pos) malignant B-cells, but not of CD20(neg)/CD47(pos) cells, and required no pro-phagocytic FcR-mediated signaling. Importantly, treatment with RTX-CD47 synergistically enhanced the phagocytic elimination of primary malignant B cells by autologous phagocytic effector cells as induced by therapeutic anticancer...
Peter E. van Bommel, Yuan He, Ilona Schepel, Mark A. J. M. Hendriks, Valerie R. Wiersma, Robert J. van Ginkel, Tom van Meerten, Emanuele Ammatuna, Gerwin Huls, Douwe F. Samplonius, Wijnand Helfrich, Edwin Bremer
Type I CD20 Antibodies Recruit the B Cell Receptor for Complement-Dependent Lysis of Malignant B Cells
Published in: Journal of Immunology
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10.4049/jimmunol.1600811
Human IgG1 type I CD20 Abs, such as rituximab and ofatumumab (OFA), efficiently induce complement-dependent cytotoxicity (CDC) of CD20(+) B cells by binding of C1 to hexamerized Fc domains. Unexpectedly, we found that type I CD20 Ab F(ab ‘)2 fragments, as well as C1q-binding-deficient IgG mutants, retained an ability to induce CDC, albeit with lower efficiency than for whole or unmodified IgG. Experiments using human serum depleted of specific complement components demonstrated that the observed lytic activity, which we termed “accessory CDC,” remained to be dependent on C1...
Patrick J. Engelberts, Marleen Voorhorst, Janine Schuurman, Tom van Meerten, Joost M. Bakker, Tom Vink, Wendy J. M. Mackus, Esther C. W. Breij, Stefanie Derer, Thomas Valerius, Jan G. J. van de Winkel, Paul W. H. I. Parren, Frank J. Beurskens
Target Antigen Density Governs the Efficacy of Anti-CD20-CD28-CD3 zeta Chimeric Antigen Receptor-Modified Effector CD8(+) T Cells
Published in: Journal of Immunology
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10.4049/jimmunol.1402346
The effectiveness of chimeric Ag receptor (CAR)-transduced T (CAR-T) cells has been attributed to supraphysiological signaling through CARs. Second-and later-generation CARs simultaneously transmit costimulatory signals with CD3 zeta signals upon ligation, but may lead to severe adverse effects owing to the recognition of minimal Ag expression outside the target tumor. Currently, the threshold target Ag density for CAR-T cell lysis and further activation, including cytokine production, has not yet been investigated in detail. Therefore, we determined the threshold target Ag density required to induce CAR-T cell responses using...
Keisuke Watanabe, Seitaro Terakura, Anton C. Martens, Tom van Meerten, Susumu Uchiyama, Misa Imai, Reona Sakemura, Tatsunori Goto, Ryo Hanajiri, Nobuhiko Imahashi, Kazuyuki Shimada, Akihiro Tomita, Hitoshi Kiyoi, Tetsuya Nishida, Tomoki Naoe, Makoto Murata