TAG–sparX interface

The TAG–sparX interface is a synthetic protein-protein interaction that serves as the foundational mechanism for the ARC-SparX platform, a controllable chimeric antigen receptor (CAR) T-cell therapy developed by Arcellx [1, 2]. This interface consists of a unique "TAG" derived from a cryptic epitope of human alpha-fetoprotein (AFP) Domain III and a corresponding synthetic binding receptor, known as a D-domain, expressed on the surface of antigen-receptor complex (ARC) T cells [1, 3]. By utilizing a soluble adapter protein (SparX) to bridge the T cell and the tumor cell, the platform allows for precise spatiotemporal control over T-cell activity through SparX dosing [4, 7]. The interaction is highly specific because the TAG epitope is occluded in native, circulating AFP, minimizing the risk of off-target activation by endogenous proteins [1, 4]. This modular design enables the targeting of multiple antigens, such as BCMA or CD123, by simply switching or combining different SparX proteins, thereby addressing challenges like tumor heterogeneity and antigen escape [1, 6].

Other names

ARC-SparX interactionAFP DIII-D-domain interfaceSparX-TAG interfaceTAG-binding domain interaction

The TAG–sparX interface functions as a synthetic bridge in a modular CAR-T system. The SparX adapter protein binds to tumor antigens via its antigen-binding domains and to the ARC-T cell via its TAG moiety. This interaction triggers the activation and cytolytic activity of the ARC-T cell specifically at the tumor site.