The prevalence of chronic diseases stemming from dysregulated immune responses is on the rise, affecting over 10% of the population and imposing a substantial burden on both individuals and society at large. Patients grappling with these conditions endure persistent health challenges, organ dysfunction, premature mortality, and a marked decline in their overall well-being. Societal costs in the EU alone surpass 100 billion euros annually, underscoring the urgency for effective interventions. Regrettably, current treatments often fall short in restoring immune homeostasis over the long term.
Our principal objective is to pioneer a safe and potent cell therapy utilizing genome-edited T cells. Specifically tailored to combat IgA nephropathy (IgAN), the most prevalent primary glomerulonephritis and a major contributor to end-stage renal disease lacking adequate treatment options. Our innovative approach holds promise for addressing other diseases associated with IgA, including IgA myeloma, IgA-lymphoma, and various autoimmune conditions like rheumatoid arthritis and systemic lupus erythematosus. Moreover, our methodology could serve as a blueprint for tackling disorders linked to other immunoglobulin types, such as IgG4.
While genetically modified T cell therapies have revolutionized the management of advanced hematological malignancies, their potential in severe autoimmune disease treatment is also emerging. Yet, existing gene transfer techniques relying on retroviral vectors pose risks of insertional mutagenesis and subsequent malignancy. Additionally, their complex manufacturing processes inflate costs in cell therapy production. Leveraging genome editing facilitates precise gene targeting, potentially mitigating oncogenic hazards and enhancing the long-term safety profile of genetically modified T cell products. Non-viral genome editing presents a cost-effective avenue for cell therapy manufacture. Within the geneTIGA project, we will meticulously assess and compare genome editing strategies for T cell redirection using synthetic antigen receptors, ensuring both efficacy and safety. Our overarching goal is to establish robust and reproducible techniques applicable not only to T cell products but also to broader gene therapy endeavors.
Ultimately, our aim is to engineer a "living drug" capable of providing a singular therapeutic intervention for IgAN and related conditions, ready for clinical evaluation. Furthermore, our initiative provides tools and technologies poised to accelerate the advancement of next-generation gene and cell therapies across diverse medical fronts.
