Team: Tanja de Gruijl, Juan Garcia Vallejo, Yvette van Kooyk, Marjolein van Egmond
A derailed immune response is a hallmark of many pathologies, in particular cancer, neurological disorders, as well as chronic inflammatory and autoimmune diseases. In the past decade, cancer immunotherapy (IT) has raised enormous expectations due to proven clinical efficacy in an ever growing number of tumor types. This has led to several anti-cancer ITs, mostly based on the inhibition of immune checkpoints such as PD-(L)1, CTLA4, and LAG3, that are rapidly becoming part of standard clinical practice in medical oncology, but also the development of CAR-T cell therapies, and a variety of vaccination modalities. Despite this success, a majority of patients do not experience clinical benefit from IT and some tumor types so far have not proven
amenable to IT at all. Innovative research is needed to understand the suppressive mechanisms that tumors impose on the immune system, and to identify biomarkers predicting therapy response and/or the development of immune-related adverse events (irAE).
IT is also relevant in neurological diseases, not only in autoimmune disorders such as multiple sclerosis and other less frequent peripheral nerve autoimmune disorders, but also more recently in Alzheimer’s disease. Immune modulation in autoimmune neurological diseases has traditionally involved step-wise introduction/escalation of immunosuppressive drugs until clinical response is achieved. This highlights the needs for the identification of biomarkers for early response prediction and immune monitoring protocols in order to minimize adverse effects of the medication and prevent non-reversible progression of the underlying neurological disease. This also applies to Alzheimer’s disease, in which we are still in an early phase to identify which patients can benefit from IT and when is the right time to initiate the IT.
Immune monitoring is the process of assessing upfront and therapy-induced immune responses in patients. Here, we propose to organize a centralized immune monitoring unit to facilitate integration of immune monitoring workflows in clinical trials and to enhance our understanding of disease processes, provide insight in mechanisms-of-action underlying therapy efficacy, and help identify novel therapeutic targets as well as predictive biomarkers for patient stratification. As such it will improve patient care and enhance the chances of a durable clinical tumor response.
The primary objective of this project is to create an infrastructure to allow the integration of immune monitoring in clinical trials for cancer and neurological diseases at Adore. The specific objectives include:
- To develop harmonized immune monitoring pipelines for clinical research.
- To establish standardized logistics and immune monitoring pipelines, comprising sample handling and collection, as well as phenotypic and functional assay development, data analysis, and reporting.
- To determine the immune modulating effects of IT in the context of well-defined patient cohorts participating in clinical trials, and relate these to efficacy and side effects in order to identify overarching immune signatures and response patterns in cancer and neurological diseases.
