TAG epitope on Soluble Protein Antigen-Receptor X-linker (SparX) protein (TAG)

The TAG epitope on the SparX protein is a central component of the ARC-SparX platform, a modular and controllable chimeric antigen receptor (CAR) T-cell technology developed by Arcellx [1.2.1, 1.2.5]. The TAG is a 26 kDa protein fragment derived from Domain III of human alpha-fetoprotein (hAFP) [1.2.4, 1.3.1]. It is engineered into a soluble adapter molecule known as a SparX (Soluble Protein Antigen-Receptor X-linker) protein, which also contains a targeting domain specific to a tumor-associated antigen [1.2.1, 1.3.1]. The TAG epitope serves as the binding site for a universal Antigen Receptor Complex (ARC) expressed on the surface of engineered T cells (ARC-T cells) [1.2.5, 1.3.2]. When the SparX protein binds to a tumor cell, it \"tags\" the cell for destruction by ARC-T cells, forming a tri-molecular complex that triggers T-cell activation and cytolytic activity [1.2.2, 1.2.5]. A key safety feature of this system is that the specific epitope on the TAG is occluded in the native, full-length hAFP molecule, preventing ARC-T cells from targeting healthy tissues that might express AFP [1.2.1, 1.2.2]. This platform allows clinicians to control the intensity of the immune response by adjusting the dose of the SparX protein and to address tumor heterogeneity by administering different SparX proteins targeting various antigens [1.2.4, 1.3.2]. Clinical applications of this technology include the treatment of relapsed or refractory multiple myeloma and acute myeloid leukemia [1.2.1, 1.3.2].

Other names

Alpha-fetoprotein Domain III TAGhAFP DIII TAGSparX adapter epitopeAFP-derived TAGAFP-DIII

The TAG epitope acts as a molecular bridge that enables a universal Antigen Receptor Complex T cell (ARC-T) to recognize and bind a soluble SparX adapter protein, which is itself bound to a tumor-associated antigen, thereby inducing T-cell activation and tumor cell lysis.