Antigen-specific treatments to target autoimmune kidney diseases

Introduction

Chronic kidney disease (CKD) affects around 10% of the population worldwide and is associated with significant overall and cardiovascular mortality. CKD is a heterogeneous group of disorders characterized by alterations in kidney structure and function and is progressive in nature.

Causes of CKD

Autoimmune diseases are a common cause of CKD and are responsible for its most aggressive and progressive forms, mainly in younger patients. Autoantibodies play major pathogenic roles in most of these disorders, and multiple disease-specific target antigens have been identified. This has shifted treatment strategies from largely unspecific immunosuppression towards B and plasma cell-targeted therapies.

Treatment Challenges

However, such treatments still involve broad immunosuppression with potentially severe adverse effects. Hence, there is a huge gap between the increasing insights into the immune mechanisms and the pathogenic role of autoantibodies against cellular antigens on one side, and the currently available treatments with limited specificity on the other side.

Vision of AUTO-TARGET

The vision of AUTO-TARGET is the development and experimental implementation of pathogenesis-based and antigen-specific treatments for autoimmune diseases of the kidney.

Objectives

The objectives are:

1. To identify and characterize novel molecular targets on autoantibody-secreting cells.
2. To target autoreactive B and plasma cells using nanobody-based compounds.
3. To engineer chimeric autoantibody receptor NK and T cells for the treatment of different autoimmune diseases of the kidney.

Translational Approach

AUTO-TARGET revolves around a highly translational approach, combining target identification and characterization in patients with autoimmune kidney diseases with unique in vitro and in vivo systems to model disease and validate therapeutics.

Implications for Patients

These translational studies pave the way for more specific, less toxic treatments and thus may represent a huge step forward for the large and growing population of patients with kidney disease.