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.
Type I CD20 Antibodies Recruit the B Cell Receptor for Complement-Dependent Lysis of Malignant B Cells
Published in: Journal of Immunology
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
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
