The medical priority Immunity & Inflammation investigates immune responses to develop novel diagnostics, targeted therapies and personalized medicine and to prevent unwanted side effects from transfusion of blood cells or products.
Coordinator: Theo Rispens PhD
Development of strategies to overcome unwanted immunity and inflammation associated with transfusion of blood products
Transfusion of blood products entails a risk for unwanted immunity and inflammation, which includes vascular inflammation, RBC and platelet alloimmunity, and Graft versus Host Disease. We aim to unravel the multifactorial processes involved in development of unwanted immune responses to understand both underlying causes and eventual consequences. We aim to actively develop implementable novel strategies or tools to better monitor and predict immune responses to blood products, and prevent or overcome consequences of other undesired immune responses such as towards the vasculature (e.g. TRALI). This includes structural and functional characterization of the antibodies, complement and immune cells involved in these responses, causing tissue damage, organ dysfunction and/or blood cell destruction. Furthermore, we investigate which factors drive early and late humoral and cellular immune responses on the one hand, and which factors are instrumental in long term tolerance induction on the other hand.
Boosting or inhibiting immunity and inflammation using blood products
Blood is a rich source of cellular and molecular components that can modify immunity and inflammation. Sanquin is one of the expertise centers to offer blood products for therapy. We aim to improve and develop novel therapies that make use of blood-derived components to treat specific pathology, including but not restricted to infectious diseases (granulocyte transfusions), autoimmune disease (antibody therapies, Tregs, tolerogenic red blood cells), peptide drug refractoriness and transplant rejection (Tregs). Development of these therapies will be based on insights obtained in mechanistic studies and immunomonitoring in the context of infectious diseases, immunodeficiencies, allo- and autoimmunity, to understand factors determining longevity of antibody responses. Furthermore, we continue to develop cell-based immune therapies from hematopoietic cells, including granulocytic phagocytes, T cells or engineered erythrocytes to either induce or reduce cellular cytotoxic adaptive immunity (e.g. in transplantation or transfusion-associated adverse reactions) .
Immune profiling of donor and patient for development of targeted therapies and personalized medicine
To ensure maximal safety for blood donors, we aim to expand immune surveillance of blood donors. We intend to develop assays to measure full blood immune cell profiles to relate immune cell subsets or whole blood omics (including proteomes and transcriptomes) to serological or clinical parameters of immunity or disease as well as e.g. age categories and life-style aspects. Hereby we aim to predict high-risk groups in infectious disease (e.g. COVID-19), inflammation, and autoimmune disease, and to develop test strategies and prediction models for improved diagnostics and optimized and personalized immune targeting.
Our ambition for the next 5-8 years is to have developed at least one novel strategy/therapy to prevent unwanted immune responses associated with transfusion of blood products, at least one novel cellular blood product, and a novel diagnostic tool or algoritm to predict development of unwanted antibody responses in people receiving blood transfusion or biologics.