Group of Arnon Kater

Immunohematology

Professor Arnon Kater, a leading figure in the field of hematology, serves as the deputy head of the Department of Hematology at Amsterdam University Medical Centers (Amsterdam UMC) and is a professor of Translational Hematology at the University of Amsterdam. His research, particularly in chronic lymphocytic leukemia (CLL), bridges the gap between fundamental scientific discoveries and clinical applications, significantly advancing our understanding and treatment of this complex disease.

Arnon Kater

Translational Research:

Professor Kater's translational research, conducted in collaboration with Professor Eric Eldering, is deeply embedded in the Laboratory of Experimental Immunology at Amsterdam UMC. Together, they focus on the intricate interactions between tumor cells and the adaptive immune system within the tumor microenvironment. Their pioneering studies have shed light on how CLL cells manipulate their surroundings to evade therapeutic interventions and immune responses. This research has led to the identification of high-risk genetic alterations and novel immune evasion mechanisms, providing a deeper understanding of the disease's pathology.

A significant aspect of his work involves exploring the role of immunometabolism in T cell dysfunction. Supported by prestigious grants like the ERC Consolidator Grant and the European Society of Hematology Grant, his team have uncovered how CLL cells impair T cells, which are crucial for cancer defense. Their research highlights the critical link between T cell signaling and metabolic processes, opening new avenues for therapeutic interventions.

Clinical Research:

Professor Kater's clinical research focuses on implementing targeted agents and engaging autologous T cells to improve patient outcomes through time-limited therapy. His clinical studies span phase 1, 2, and 3 trials, both investigator-initiated and company-sponsored, demonstrating his commitment to translating laboratory insights into practical treatments.

One of his landmark achievements is the MURANO Trial, a global phase 3 study that established the venetoclax-rituximab regimen as a time-limited, chemotherapy-free treatment for relapsed/refractory CLL. This regimen significantly improved overall survival and set a new standard of care. Similarly, his work on BTK and Bcl-2 inhibitor combinations led to the practice-changing GLOW Trial, offering a chemotherapy-free option for elderly first-line CLL patients.

Innovative Approaches:
Professor Kater is also at the forefront of developing novel bispecific antibodies in combination with targeted agents. He is pioneering two HOVON trials in this area, aiming to further enhance treatment efficacy and patient outcomes.

Through his groundbreaking research, Professor Kater has not only transformed CLL treatment paradigms but also broadened the impact of his findings to other B-cell malignancies.

Group members

Groupleaders:

Eric Eldering
Arnon Kater
Maria Themeli

Postdocs:

Fleur Peters,
Armando van Bruggen,
Helga Simon-Molas,
Marco Haselager

PhD’s:

Nienke Goedhart
Chaja Jacobs
Elena Camerini
Demi Both,
Carlota López Sánchez

Technicians:

Gaspard Cretenet,
Joanne Rietveld,
Morris Mes,
Jamie Lee Roos,
Ingrid Derks,
Marjolein Dijkema

Biobank:

Julie Dubois, head
Dennis de Rooij, technician
Ilse Ligtenberg, technician
Inoka Twickler, technician

Trialbureau:

Marije Faber, overall head
Cheyenne Pierie, head CLL program

Key publications

Clinical research:

Fixed-Duration Ibrutinib-Venetoclax in Patients with Chronic Lymphocytic Leukemia and Comorbidities
Kater AP, Owen C, Moreno C, Follows G, Munir T, Levin MD, Benjamini O, Janssens A, Osterborg A, Robak T, Simkovic M, Stevens D, Voloshin S, Vorobyev V, Ysebaert L, Qin R, Steele AJ, Schuier N, Baeten K, Caces DB, Niemann CU. NEJM Evid. 2022 Jul;1(7):EVIDoa2200006. doi: 10.1056/EVIDoa2200006. Epub 2022 May 13. PMID: 38319255.

(This pivotal study led to regulatory approval, revolutionizing first-line treatment for patients.)

Minimal residual disease-guided stop and start of venetoclax plus ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia (HOVON141/VISION): primary analysis of an open-label, randomised, phase 2 trial
Kater AP, Levin MD, Dubois J, Kersting S, Enggaard L, Veldhuis GJ, Mous R, Mellink CHM, van der Kevie-Kersemaekers AF, Dobber JA, Poulsen CB, Frederiksen H, Janssens A, Schjødt I, Dompeling EC, Ranti J, Brieghel C, Mattsson M, Bellido M, Tran HTT, Nasserinejad K, Niemann CU. Lancet Oncol. 2022 Jun;23(6):818-828. doi: 10.1016/S1470-2045(22)00220-0. PMID: 35654052.

(This investigator-initiated study, based on their own in vitro and mouse models, demonstrated personalized medicine's potential to allow treatment cessation based on cellular and molecular responses.)

Venetoclax Plus Rituximab in Relapsed Chronic Lymphocytic Leukemia: 4-Year Results and Evaluation of Impact of Genomic Complexity and Gene Mutations From the MURANO Phase III Study - PubMed (nih.gov)
Kater AP, Wu JQ, Kipps T, Eichhorst B, Hillmen P, D'Rozario J, Assouline S, Owen C, Robak T, de la Serna J, Jaeger U, Cartron G, Montillo M, Dubois J, Eldering E, Mellink C, Van Der Kevie-Kersemaekers AM, Kim SY, Chyla B, Punnoose E, Bolen CR, Assaf ZJ, Jiang Y, Wang J, Lefebure M, Boyer M, Humphrey K, Seymour JF. J Clin Oncol. 2020 Dec 1;38(34):4042-4054. doi: 10.1200/JCO.20.00948. Epub 2020 Sep 28. PMID: 32986498; PMCID: PMC7768340.

(This study advanced treatment by matching molecular profiles with therapies, enhancing prediction accuracy and treatment efficacy.)

Venetoclax-Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia
Seymour JF, Kipps TJ, Eichhorst B, Hillmen P, D'Rozario J, Assouline S, Owen C, Gerecitano J, Robak T, De la Serna J, Jaeger U, Cartron G, Montillo M, Humerickhouse R, Punnoose EA, Li Y, Boyer M, Humphrey K, Mobasher M, Kater AP. N Engl J Med. 2018 Mar 22;378(12):1107-1120. doi: 10.1056/NEJMoa1713976. PMID: 29562156.

(This pivotal study led to the approval and provided the first evidence supporting the transition from chemotherapy to fixed-duration targeted treatment.)

Preclinical / translational research:

Chronic lymphocytic leukemia presence impairs antigen-specific CD8+ T-cell responses through epigenetic reprogramming towards short-lived effectors
Martens AWJ, Kavazović I, Krapić M, Pack SM, Arens R, Jongejan A, Moerland PD, Eldering E, van der Windt GJW, Wensveen FM, Peters FS, Kater AP. Leukemia. 2023 Mar;37(3):606-616. doi: 10.1038/s41375-023-01817-z. Epub 2023 Jan 19. PMID: 36658390; PMCID: PMC9851097.

(This in vitro and mouse model study provides the first evidence that leukemia cells epigenetically modify T cells, resulting in T cell dysfunction.)

A Bispecific Single-Domain Antibody Boosts Autologous Vγ9Vδ2-T Cell Responses Toward CD1d in Chronic Lymphocytic Leukemia
de Weerdt I, Lameris R, Ruben JM, de Boer R, Kloosterman J, King LA, Levin MD, Parren PWHI, de Gruijl TD, Kater AP, van der Vliet HJ. Clin Cancer Res. 2021 Mar 15;27(6):1744-1755. doi: 10.1158/1078-0432.CCR-20-4576. Epub 2021 Jan 15. PMID: 33451981.

(This study, building on the group's prior in vitro research, developed a novel therapeutic agent targeting a rare T cell subset for cancer treatment, now undergoing clinical trials.)

Chronic lymphocytic leukemia cells impair mitochondrial fitness in CD8+ T cells and impede CAR T-cell efficacy
van Bruggen JAC, Martens AWJ, Fraietta JA, Hofland T, Tonino SH, Eldering E, Levin MD, Siska PJ, Endstra S, Rathmell JC, June CH, Porter DL, Melenhorst JJ, Kater AP, van der Windt GJW. Blood. 2019 Jul 4;134(1):44-58. doi: 10.1182/blood.2018885863. Epub 2019 May 10. PMID: 31076448; PMCID: PMC7022375.

(This highly cited study provided the first global evidence of metabolic alterations in CLL patients' T cells, revealing the basis for acquired dysfunction and sparking a fruitful research line.)

Contact

+31 20 44 42604
a.p.kater@amsterdamumc.nl | assistant.kater@amsterdamumc.nl

Keywords

Cancer Center Amsterdam