Peperzak lab
@ The University Medical Center Utrecht (UMCU), Netherlands
B cell malignancies
Research aim
Our research aim is to control cellular life and death decisions to improve treatment of B cell cancers and allow T cell immunotherapy for untreatable cancers.
About us
The background of our research concerns cell death regulation in T and B lymphocytes. With previous interests and expertise we developed two main research lines; 1) targeting malignant B cells to improve patient treatment and 2) designing an enhanced killing machinery for engineered T or NK cells. We work in close collaboration between the center for translational immunology (CTI) and hematology department at the UMC Utrecht and combine fundamental research questions with (pre)clinical implementation. Our main focus relates to improving treatment of the incurable plasma cell malignancy multiple myeloma (MM), but we also focus on other B cell malignancies including classical Hodgkin lymphoma (HL), B-cell non-Hodgkin lymphoma (NHL) and amyloid light-chain (AL) amyloidosis. Next to combination therapy with small molecule inhibitors we employ different strategies to enhance effectivity of cellular immunotherapy. As a means to achieve this we use biochemical & cell engineering approaches, animal models and 3D culture with primary material.
B cell malignancies team
Curiosity drives us, Persistency defines us
Victor obtained his PhD in 2010 at the Netherlands Cancer Institute (NKI) in Amsterdam examining the mechanisms of T cell co-stimulation. He subsequently moved to the Walter and Eliza Hall Institute (WEHI) in Melbourne, Australia, as a postdoctoral fellow to study pro-survival BCL-2 family proteins in healthy B and plasma cells. This research line was continued at the Academic Medical Center (AMC) in Amsterdam focusing on malignant B cells. Since 2016 he leads this research team at the UMCU.
Marta is originally from Spain, where she graduated in Pharmacy and obtained her PhD in Immunology (University of Barcelona). During her PhD, she studied the inhibitory receptor SLAMF3 as a potential target for the treatment of autoimmune diseases and B cell malignancies. In 2017 she received a postdoctoral grant (Ramón Areces foundation) and joined the group of Victor Peperzak at the UMCU. Here, she developed diverse hydrogel-based culture systems for patient-specific drug sensitivity profiling in multiple myeloma, which can be applied to investigate optimal treatment sequencing strategies. In 2022 she was awarded a Young Investigator Grant from the Dutch Cancer Foundation (KWF), and her current research focuses on improving CAR-T cell cytotoxicity against hematological cancers. Besides her research and teaching activities, Marta is an active member of the Early Career Research board at the UMCU.
Benjamin, originally from France, began his academic journey with an Erasmus MSc internship at the Jagiellonian University of Krakow, where he developed a keen interest in gene engineering. Following this, he pursued a PhD in the Blood Cancer Research Group at Ostrava, Czechia, where his research focused on developing allogenic natural killer-cell based immunotherapies for hematological malignancies. After completing his PhD in 2023, Benjamin was hired as postdoctoral fellow within the Peperzak group and is currently working on optimizing CAR-T cell therapies based on the team's proprietary OK-tech patent.
After obtaining her BSc degree in 2004, Dedeke has been a research technician in several labs, initially in the field of infectious diseases starting in the Netherlands, but continuing her research overseas in the United States. In 2014, she returned to the Netherlands to continue her work in vaccine development, but made a switch to the field of oncology in 2019. She joined the Peperzak group in 2021 where her main focus lies with the project of Marta Cuenca to reveal important pathways that MM cells use to escape therapy and finding ways to target these specific pathways.
With an affinity for biology Ralph obtained his BSc degree in 2011 at the Hogeschool Utrecht, specializing in zoology, and his Master degree at the University of Utrecht in 2014. During his internships Ralph laid the groundwork for a broad base of different animal models and techniques which he expended as research technician in the group of Tim Radstake within the Centre for Translational Immunology (CTI) of the UMCU. After disbanding of the research group, Ralph continued research within the CTI but made a switch to the field of oncology in 2020 in the group of Jeanette Leusen. In 2022 Ralph joined the Peperzak group with his main focus on the project of first Thomas Kimman, and now Corine Pleijte, which entails the quest to enhance the killing ability of BCMA CAR T cells for treatment of multiple myeloma.
Flores obtained his medical degree from the Erasmus University in Rotterdam. Besides running and cycling, he developed a passion for onco-hematology during his internships. “Guiding patients through challenging periods of hospital visits and intensive treatments is valuable and interesting,” To launch his scientific career, he began working at UMC Utrecht, where he set up a retrospective myelofibrosis cohort. Currently, he is studying AL amyloidosis as a PhD student. His project focuses mainly on the epidemiological aspects of AL amyloidosis in collaboration with the Netherlands Cancer Registry. Additionally, he is pursuing a master’s degree in epidemiology at Utrecht University. In the lab, he aims to predict which patients may benefit from venetoclax-based therapy.
Corine began her medical degree in 2015 at Utrecht University. During her studies, she developed a strong interest in translational research and undertook various internships, primarily in oncology. After a year of clinical work in internal medicine, she is now a PhD student focused on developing a novel technique to enhance the killing ability of BCMA CAR T cells for treatment of multiple myeloma.
Originally from Romania, I moved to the Netherlands in 2017 to obtain a Biomedical BSc in Maastricht and an Infection and Immunity MSc at Utrecht University, meaning that I have officially lived in the Netherlands now for around a quarter of my life. My project focuses on identifying more specific treatment strategies for pediatric Hodgkin lymphoma. To do this, we aim to better understand the interactions between the very rare tumor cell population and the other immune cells in the microenvironment, with a special emphasis on CD4+ T cells.
After obtaining her BSc in Biology at the University of Genova in 2020, Eugenia moved to The Netherlands and graduated from her MSc in Cell Biology and Molecular Interactions at the Wageningen University & Research in 2023. During her internships and studies, she developed a strong interest in the field of OncoImmunology. She joined the Peperzak group in 2024 where she is currently pursuing a PhD centered on the design of 3D culture models with primary cells to test novel immunotherapeutic approaches.
Originally from Finland, Toni earned his BSc in Biomedical Laboratory Science from Oulu University of Applied Sciences in 2022. During and after his studies, he worked in various diagnostic laboratories at Oulu University Hospital. Soon after graduating, Toni sold everything but his books and moved to the Netherlands to join a Developmental Biology research group at Utrecht University. In 2024, he joined the Peperzak group, where he now contributes to Diana Petcu’s project focused on developing more targeted treatment strategies for pediatric Hodgkin lymphoma.
Valke is a first-year intern from the Master Infection and Immunity. After completing a BSc in Biomedical Sciences at Utrecht University, she pursued her interest in the immunity research field and started her internship at the Peperzak group. Together with her supervisor Marta, she researches improving CAR-T cell cytotoxicity against multiple myeloma.
I’m Maiken, a recent graduate with a bachelor’s in Biomedical Sciences from Utrecht University, now pursuing my master’s in Infection and Immunity. My passion for immunology led me to join the Peperzak group, where I’m currently a first-year intern. Under the guidance of my supervisor, Benjamin, I’m working on advancing CAR-T cell therapies using the team’s innovative OK-tech patent. I’m excited to see what we can accomplish together in the coming months!
Alumni
Felicia Amelie (2023 - 2024) - MSc internship
Lieke Gol (2022 - 2023) - MSc internship
Manuel Beltran (2022) -visiting PhD student
Wendy Boschloo (2021 - 2022) - MSc internship
Patrick Greve (2020 - 2023) - MD/PhD student
Leonie Abbink (2019 - 2020) - MSc internship
Niels van Nieuwenhuijzen (2019 - 2023) - MD/PhD student
Sarah Grabherr (2018 - 2019) - MSc internship
Thomas Kimman (2018 - 2023) - PhD student
Laura Timmerman (2018 - 2019) - Technician
Luke Faber (2017 - 2018) - MSc internship
Douwe Bosma (2017 - 2018) - MSc internship
Ingrid Spaan (2016 - 2021) - PhD student
Sanne Kroos (2016 - 2017) - MSc internship
Laura Moesbergen (2016 - 2021) - Sr Technician
Anne Slomp (2016 - 2020) - PhD student
selected
Publications
Identifying clinical response to daratumumab therapy in relapsed/refractory multiple myeloma using a patient-derived in vitro model. van Nieuwenhuijzen N, Cuenca M, Abbink L, Jak M, Peperzak V, Minnema MC.
EJHaem. 2023 Nov 29;5(1):141-146. PMID: 38406516
Serpin B9 controls tumor cell killing by CAR T cells. Kimman T, Slomp A, Martens A, Grabherr S, Li S, van Diest E, Meeldijk J, Kuball J, Minnema MC, Eldering E, Bovenschen N, Sebestyén Z, Peperzak V.
J Immunother Cancer. 2023 Mar;11(3):e006364. PMID: 36931661
Targeting B-cell maturation antigen increases sensitivity of multiple myeloma cells to MCL-1 inhibition. Cuenca M, Van Nieuwenhuijzen N, Moesbergen LM, Bloem A, Minnema MC, Peperzak V.
Haematologica. 2022 Apr 1;107(4):980-983. PMID: 34879645
Direct P70S6K1 inhibition to replace dexamethasone in synergistic combination with MCL-1 inhibition in multiple myeloma. Spaan I, Timmerman LM, Kimman T, Slomp A, Cuenca M, van Nieuwenhuijzen N, Moesbergen LM, Minnema MC, Raymakers RA, Peperzak V.
Blood Adv. 2021 Jun 22;5(12):2593-2607. PMID: 34152396
Phosphatase PP2A enhances MCL-1 protein half-life in multiple myeloma cells. Slomp A, Moesbergen LM, Eldering E, Kersten MJ, Minnema MC, Peperzak V.
Cell Death Dis. 2021 Mar 3;12(3):229. PMID: 33658484
Multiple myeloma with 1q21 amplification is highly sensitive to MCL-1 targeting. Slomp A, Moesbergen LM, Gong JN, Cuenca M, von dem Borne PA, Sonneveld P, Huang DCS, Minnema MC, Peperzak V.
Blood Adv. 2019 Dec 23;3(24):4202-4214. PMID: 31856269