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Background and research lines

Development of haematological malignancies is only possible upon escape of malignant cells from immune surveillance by both innate and adaptive immune cells. Cancer cells have acquired many features that can silence immunity, e.g., by upregulating so-called immune checkpoints (brakes on immune cells) or by altering their ‘sugar coat’ on the cell surface to prevent recognition and elimination. Nevertheless, presence of immune cells, most notably T cells, in the tumour micro-environment still associates with better survival in many cancers. Therefore, elucidation and targeted (re)activation of anticancer immunity is of clear therapeutic interest. Indeed, the two major breakthroughs in cancer therapy in the past decade, immune checkpoint inhibitors and Chimeric Antigen Receptor (CAR) T cell therapy, are strategies that restore effective cancer control by immune cells. Both these strategies yield durable complete responses in previously end-stage patients.

Our central research tenet is the development of innovative cancer immunotherapeutics, with several dedicated research lines. Within the first research line, novel immune checkpoint therapeutics are being designed and evaluated, with a particular focus on (re)activation of innate immune responses. The second research line is focussed on the development, improvement and implementation of CAR-T cell therapy, most notably Point-of-Care CAR-T cell therapy. Hereto, we lead a large national phase II clinical trial for relapsed/refractory Diffuse Large B cell lymphoma (HOVON161). Moreover, we are developing new CAR-T concepts for PoC implementation (e.g., for T cell lymphoma and AML) and are implementing CAR concepts in alternate immune cell populations. The third research line is aimed at defining cancer-specific sugar (or glycosylation) changes that enable immune escape of cancer cells and associate with aggressive disease. Based on these insights, we aim to develop diagnostic tools and therapeutic strategies that target these sugar changes.

Our research spans from target identification/validation and design of novel immunotherapeutics to preclinical proof-of-efficacy studies and clinical implementation of therapeutics, as well as screening of unique patient data sets/biobanks to drive research in a bedside-to-bench and back manner. Indeed, our research efforts hinge on a close collaboration between clinical and basic scientists and is comprised of a preclinical translational laboratory and a dedicated clinical laboratory for the PoC production of CAR-T and standard-of-care hematopoietic stem cell therapy.

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