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.