Over the past decades, the life expectancy of the Dutch population increased. With it, the incidence of cancer is also steadily increasing. Even though substantial improvements were achieved in the standard care of cancer patients, the mortality and morbidity for certain forms of cancer is still unchanged. Thus, there is a need for alternatives to the existing therapies. This includes the production of top-quality transfusion products, and the development of diagnostic tools for e.g. minimal residual diseases, and for medicinal dosing. Moreover, therapies need to be affordable to make them widely accessible to the patients.
Sanquin Research & Labservices houses the Laboratory for Cellular Therapy (LCT) including the Dutch cord blood bank which provides units for transplantation world-wide, and that processes and stores hematopoietic stem and progenitor cells (HSPC) for transplantation into patients with (hematological) malignancies. In addition, GMP-grade tumor-infiltrating Lymphocytes (TILs), CAR T cells and MSCs are generated and/or processed of which some are currently used in clinical trials at the Dutch Cancer Institute, and the Amsterdam University Medical Center. Because the LCT is embedded in the research division, research findings can be readily implemented to cell-based products. Sanquin Diagnostics services such as HLA-typing for donor matching and (immune) therapy monitoring complement or efforts to generate and improve blood cell products for clinical use, and for diagnostics for minimal residual diseases (MRD) for leukemia’s and neuroblastoma. Dual appointments to both departments and the close interactions with the diagnostics department and the LCT allow for rapid implementation of research findings.
Our fundamental research questions are aimed at improving diagnostic tools and cellular products for cancer patients. Many research lines are formulated together with our clinical partners. Addressing fundamental questions in tumor immunology and tumor biology funded by external grants paves the way for novel leads in product development. The strong collaborations between different research groups and the close interactions with Research and LCT/Diagnostics/Reagents substantially contributes to the scientific knowledge. It is also required to develop and optimize in-house services and products. Continuous internal support through continuous investments into core facilities is key to sustain high quality research and to attract excellent talents to Sanquin. With this unique setup, Sanquin can be at the forefront of scientific advances and in product development, and at the forefront of FAIR MEDICINE. We can thus contribute to the development of affordable immunotherapy treatments that are widely accessible to patients.
Coordinators: Monika Wolkers PhD, Prof Mette Hazenberg MD PhD
T cell biology
T cells can be effectively exploited for therapeutic purposes. To develop and improve T cell therapies, one needs to define 1) which T cell populations are the best effector cells against cancer 2) what defines effective T cell responses and 3) how we can boost and maintain T cell responses against cancer. With these basic research questions T cell therapies are developed together with the LCT, such as TIL therapy for non-small cell lung cancers.
Therapeutic antibodies is a prime focus for immunotherapies, yet the clinical outcome does not always meet the expectations. We study natural structural-and functional variations in human antibodies, including glycosylation. This knowledge will be used to engineer antibodies with increased efficacy. We also monitor the therapeutic use and/or dosing of antibodies.
Neutrophils are the most abundant immune cell type and can be targeted for immunotherapy. Efforts to mobilize neutrophil-mediated tumor cell killing is the prime focus.
Opportunities and threats of transplantation in malignancies
Allogeneic HSPC transplantation is an important means to treat leukemia, yet it also induces GvHD. Unraveling the fundamental basics of GvHD is critical to identify possible means to reduce the risk thereof without losing its therapeutic anti-tumoral potential. Moreover, adoptive therapies to prevent or mitigate GvHD are being developed. We also study the homeostatic and regenerative bone marrow (BM) environment, in particular interactions between hematopoietic and stromal cells, to develop optimized treatment strategies for the patients.
MRD detection in childhood cancers
PCR based screens, digital droplet PCR and NGS-based assays on cell free tumor DNA, allow the detection of MRD. This method is now routinely used by Diagnostics for ALL patients and in development for neuroblastoma and rhabdomyosarcoma patients.