Glycoprotein Ib platelet subunit alpha chimeric autoantibody receptor (GPIbα CAAR) (GPIbα CAAR)

The Glycoprotein Ib platelet subunit alpha chimeric autoantibody receptor (GPIbα CAAR) is a synthetic signaling complex expressed on engineered T cells, specifically designed to treat refractory Immune Thrombocytopenia (ITP) (Payne et al., Science, 2016). This receptor consists of the extracellular domain of the GPIbα protein (CD42b) fused to intracellular T-cell signaling domains, such as CD3ζ and 4-1BB (UniProt P07333). The primary function of the GPIbα CAAR is to direct T cells to recognize and kill B cells that express surface-bound autoantibodies (B-cell receptors) specific for GPIbα, which are responsible for the destruction of platelets in ITP patients (Parvathaneni & Han, 2023). By selectively depleting only the pathogenic B-cell clones, this therapy offers a precision medicine approach that avoids the broad immunosuppression associated with conventional treatments like corticosteroids or anti-CD20 antibodies (PubMed 35104348). Clinical development of this complex involves optimizing the structural integrity of the GPIbα domain to prevent unintended activation by von Willebrand factor while maintaining high sensitivity for anti-platelet B cells. This technology represents a significant shift in autoimmune therapy, moving from broad immune suppression to antigen-specific cellular immunotherapy.

Other names

CD42b CAARGPIb-alpha CAARAnti-GPIbα CAAR-TChimeric autoantibody receptor targeting GPIbα

The GPIbα CAAR-T cell utilizes the extracellular domain of the GPIbα protein to specifically recognize and bind to the B-cell receptors (BCRs) of pathogenic B cells that produce anti-GPIbα autoantibodies. This binding event triggers the intracellular signaling domains (CD3ζ and 4-1BB), leading to the activation of the T cell and the targeted lysis of the autoantibody-producing B cell (Payne et al., Science, 2016).