Cancer Center Amsterdam

Exploration of a differential blood platelet subpopulation in the thrombocytopenic glioblastoma patient

Patients with a glioblastoma, one of the most aggressive primary brain tumors, face a dismal prognosis and should receive optimal treatment. A common complication of the chemotherapeutic treatment temozolomide is the development of significantly reduced blood platelets, termed thrombocytopenia. This condition urges the neuro-oncologists to stop temozolomide treatment preliminary, thereby having a suboptimal therapy effect and potential negative consequences on the patient’s survival. The aim of this project is to identify a blood platelet-based biomarker that predicts at start of the treatment course the development of such a deficiency in blood platelets. If this proves to be successful, such a biomarker test may ultimately guide temozolomide precision dosing, reducing the risk of developing severe thrombocytopenia.

Myron Best | Postdoctoral researcher Neuro-oncology | Resident neurosurgery (AIOS)

Mapping the functional anatomy of the tumor-brain interface to discover novel treatment avenues for IDH-mutant glioma

With the help of the CCA 2024 grant, we will investigate the intricate relationship that IDH-mutant glioma tumors maintain with the surrounding brain tissue. We will use spatial transcriptomics in combination with multi-electrode array recordings and extensive histology on patient brain tissue to analyse how tumor-brain interactions affect tumor growth and symptomatology. Combining knowledge from both oncology and neuroscience, we hope to make significant advances that may lead to the discovery of novel treatment avenues.

Dorien Maas | Assistant Professor | Anatomy and neurosciences

Mapping functional APC-T cell interactions in the tumor microenvironment – the power of the cluster method

In this project, I will explore how antigen-presenting cells (APCs)
interact with T cells in the tumor microenvironment, affecting cancer
progression and treatment responses. Using an innovative approach that combines
spectral- and imaging-flow cytometry with single-cell RNA sequencing, I can
analyse these interactions across entire tumor biopsies. By identifying
critical receptor-ligand interactions, such as the sialic acid-Siglec axis, my
work aims to uncover mechanisms of immune suppression and activation to,
ultimately, improve immunotherapy strategies for lung cancer patients.

Sofía Ibáñez Molero | Postdoctral researcher | Molecular Cell Biology & Immunology

The impact of the gut microbiome and its metabolites on tumor-specific immunity against acute myeloid leukemia

Alexander de Porto's project investigates how gut bacteria (microbiome) and the substances they make (metabolites) affect the immune response against a form of bone marrow cancer, acute myeloid leukemia (AML). An adequate immune response is important for complete clearance of malignant cells and is thus an important predictor of survival for patients with AML. It is known that the microbiome and its metabolites influence the immune system, but how exactly is unknown. By using advanced “multi-omics” techniques, Porto hopes to find clues for the development of new treatment strategies against AML that target the microbiome.

Alexander de Porto | Resident internal medicine | Postdoctoral researcher | Clinical Hematology

Comprehensive CRISPR/Cas9 tiling of a human chromosome

A deep functional understanding of the human genome remains a significant and complex challenge. To date, most efforts to decipher its function have primarily focused on annotated protein-coding genes. However, the recent discovery of over 43,000 non-coding RNA genes (Gencode V47) underscores the pressing need for a broader exploration of the genome’s functional landscape. In this context, we aim to leverage our recently awarded CCA grant to begin the systematic exploration of all essential elements of the human genome by performing CRISPR/Cas9 tiling across an entire chromosome. Our goal with this proof of concept is to identify a broad spectrum of essential elements—both known and new—in an unbiased manner. While this is a monumental undertaking, mapping these essential genomic components across various cellular contexts represents a critical step in advancing our understanding of the human genome."

Oscar Bril | PhD student | Center of Experimental and Molecular Medicine

Non-invasive, accessible liver function assessment with quantitative MRI to guide hepatectomy in hepatic cancer

Surgical removal of hepatic cancer is the only curative treatment, but removing a significant portion of the liver risks liver failure. To mitigate this, liver function must be assessed. This study investigates whether quantitative MRI can measure the liver function in these patients and whether they are able to detect underlying liver diseases as well. If successful, quantitative MRI could replace current methods, simplifying workflows and minimize patient burden. This CCA grant has been granted to Nienke Wassenaar, a technical physician, in collaboration with dr. Oliver Gurney-Champion, dr. Joris Erdmann and prof. dr. Joanne Verheij.

Nienke Wassenaar | PhD student | Radiology and Nuclear medicine

Contrast-enhanced ultrasound (CEUS) for early differentiation between malignant sarcomas and benign myomas in the uterus

In the clinic, fibroids (benign tumors) and sarcomas (malignant tumors) of the uterus are difficult to distinguish. Our project aims to evaluate whether we can make the difference clearer make the difference clearer with a contrast echo (CEUS). With the CEUS, intravenous extremely small gas bubbles to image the microvascular buildup of tissue. We will examine the ultrasound images qualitatively, as well as correlate them to the histology and perform quantitative analysis of the images in collaboration with TU Eindhoven. In doing so, we hope to improve the care of women with suspected a sarcoma in the future and to avoid over- or under-treatment.

Jenneke Kasius | Consultant gynaecologist | Obstetrics and gynaecology

Proof-of-Concept projects

First in human PET-imaging of glutamine metabolism in Chronic Lymphocytic Leukemia

Recent studies by Eldering and Kater's group have revealed metabolic reprogramming in CLL lymph nodes, demonstrating that CLL cells within lymphoid tissues can switch to glutamine metabolism to support energy demands and proliferation. This finding suggests that glutamine-based imaging techniques may offer more accurate disease monitoring in CLL compared to conventional 18F-FDG PET. With a CCA grant awarded in Dec 2020, we synthesized 4-[18F]GLN and conducted successful in vitro labelling studies of primary CLL cells. Additionally, we performed promising investigations in an in vivo murine CLL model. Based on these exciting preclinical results we propose a unique collaboration between laboratory, clinical and imaging groups of Amsterdam UMC to reach the following aims:
1. Develop 4-[18F]GLN to image in CLL patients
2. Measure therapy response and possible relapses
We will set execute a first in human study with 4-[18F]GLN to visualize and quantify 4-[18F]GLN uptake and assess CLL metabolism in relapsed CLL pts

Prof. dr. Josée Zijlstra | Professor of hematology | Department of hematology

Ben Zwezerijnen | Medical Specialist | Radiology and nuclear medicine

Prof. dr. Bert Windhorst | Professor Radiology and nuclear medicine

NON-IV study: Neo-adjuvant peritumOral immuNotherapy In Vulvar cancer

Vulvar cancer is relatively rare and may be caused by a persistent HPV infection. Primary treatment is surgery, but that can cause significant morbidity. To improve patient outcomes and reduce morbidity after treatment, there is a need for novel therapeutic strategies. In this phase 1 study we will administer a combination of Programmed-Death-1 receptor (PD-1) and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) checkpoint inhibitors locally (around the tumor), prior to surgical treatment, in early-stage vulvar cancer patients. The aim of the study is to assess the safety and toxicity of neo-adjuvant, local checkpoint inhibition in vulvar cancer, and to study the effects on the lymph node microenvironment, and on immune subsets in peripheral blood.

Jacqueline Tromp (medical oncologist), Tanja de Gruijl (head of the Immunotherapy Lab of the department of Medical Oncology), Stijn Mom (gynaecological oncologist) and Marije Strikwerda (PhD candidate).

Safety and tolerability of treating locally advanced Resectable Oral Cancer with neoadjuvant INtratumoral anti-CTLA4 ImmunoTherapy combined with systemic anti-PD-1 (ROCinIT)

Cancer Center Amsterdam approved the ROCinIT proof of concept trial. In the ROCinIT trial we will assess the safety and tolerability of treating Resectable Oral Cancer with neoadjuvant INtratumoral anti-CTLA4 combined with systemic anti-PD-1 ImmunoTherapy. This trial is the successor of the NeoNivo trial (Wondergem, Miedema et al. JITC 2024) performed within the PRG-HNO previously. In the NeoNivo phase I/II trial, neoadjuvant systemic anti-PD-1 nivolumab was administered in this patient population, and we observed major regression of the primary tumor in 19% (3/16) of the patients treated. We hypothesize that local immune suppression may have hampered a response in the non-responding patients, which is supported by other trials in which systemic anti-CTLA4 was combined with anti-PD1 but at the expense of increased toxicity. Therefore, we anticipate that adding local checkpoint inhibition with anti-CTLA4, which can target suppressive T cells in the tumor microenvironment, will increase the response rate without inducing high toxicity. With this trial we aim to further spike the revolution that immune checkpoint blockade has brought in the management of head and neck squamous cell carcinoma.

Dr. Rieneke van de Ven | Group leader Head and Neck tumor immunology

Prof. dr. René Leemans | Chair Department of Otolaryngology Head and Neck Surgery

Follow Cancer Center Amsterdam on LinkedIn & BlueSky