[CAR T cells in non-malignant diseases].

Abstract

Background: Chimeric antigen receptor (CAR) T cells specific for CD19 or B cell maturation antigen (BCMA) are now the standard treatment for relapsed/refractory B cell neoplasms. Because autoreactive B cells play a key role in the pathogenesis of autoimmune diseases (AID), it has been hypothesized that B cell-specific CAR-T cells eliminate autoreactive B cell clones via a deep depletion of B cells and lead to a reset of the immune system. Initial pilot studies with CAR T cells against CD19 in rheumatologic and neurologic AIDs have confirmed this hypothesis and led to sustained drug-free remission of the diseases.

Objective: The aim of this review article is to summarize and evaluate these novel developments.

Methods: Initial case series and results of early clinical trials on the different entities and the current understanding of the underlying new treatment concepts are presented.

Results: In a number of B cell-driven AIDs, such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc) or idiopathic inflammatory myositis (IIM), B cell-specific CAR T cell treatment was able to induce deep and sustained remission and lead to clinical improvement of organ damage. Initial successes have also been recorded in other hematologic, neurologic and dermatologic B cell-mediated AIDs. In addition, there are promising CAR T cell-based concepts for combating chronic infectious diseases, such as human immunodeficiency virus (HIV) or hepatitis B, transplant rejection and type 1 diabetes mellitus.

Conclusion: The use of CAR T cell treatment in severe forms of chronic non-malignant diseases represents a novelty in medicine and opens up groundbreaking new possibilities and concepts for treatment.