Antigen-specific B-cell receptor (BCR)

The target consists of B-cell receptors (BCRs) or surface immunoglobulins (sIg) expressed on the surface of pathogenic B cells that are specific for a particular autoantigen (Ellebrecht et al., 2016, Science). In autoimmune diseases, these specific B cells differentiate into plasma cells that produce harmful autoantibodies, leading to tissue damage (Parvathaneni & Werth, 2020, Frontiers in Medicine). Chimeric Autoantibody Receptor (CAAR) T-cell therapy is designed to exploit this specificity by expressing the autoantigen itself as the extracellular domain of a chimeric receptor (Cabaletta Bio, 2024). This allows the CAAR-T cells to selectively recognize and kill only the B cells that react to that specific antigen, while sparing the rest of the healthy B-cell population. This approach offers a precision medicine alternative to broad B-cell depletion therapies like rituximab, potentially reducing the risk of systemic immunosuppression. Current clinical applications include targeting B cells specific for Desmoglein 3 in Pemphigus Vulgaris and Muscle-Specific Tyrosine Kinase (MuSK) in Myasthenia Gravis (ClinicalTrials.gov NCT04422912). The interaction between the CAAR and the BCR triggers T-cell activation and subsequent lysis of the pathogenic B cell, aiming to eliminate the source of autoantibodies without compromising the patient's overall humoral immunity.

Other names

Surface immunoglobulinsIgAutoantigen-specific B-cell receptorPathogenic B-cell receptorAntigen-specific surface immunoglobulin

Chimeric autoantibody receptor (CAAR) T cells express the specific autoantigen on their surface; these cells selectively bind to and eliminate pathogenic B cells that express surface immunoglobulins (B-cell receptors) specific for that autoantigen through direct T-cell mediated cytotoxicity (Ellebrecht et al., 2016, Science).