Alpha-fetoprotein-derived TAG domain (ARC-tag) (ARC-tag)

The ARC-tag (Antigen-Receptor Complex tag) is a synthetic protein domain, specifically a fragment of human alpha-fetoprotein (AFP), that serves as a universal docking site within the Arcellx ARC-T platform. In this modular cell therapy system, the ARC-tag is fused to a targeting moiety to form a soluble adapter protein known as a sparX (soluble protein antigen-receptor X-linker), such as SPRX002 which targets CD123. The ARC-tag is recognized with high affinity by a synthetic receptor (the ARC) expressed on the surface of universal CAR-T cells (ARC-T cells). This interaction facilitates the formation of a tricomplex between the cancer cell, the sparX adapter, and the ARC-T cell, leading to T-cell activation and targeted tumor cell lysis. By using the ARC-tag as a standardized intermediary, the system allows for controllable and multi-antigen targeting, as the dose of the tag-containing adapter can be adjusted to manage toxicity or switched to target different antigens without re-engineering the T-cells.

Other names

TAG domainAFP-tagsparX-tagD-Domain targetAntigen-Receptor Complex tag

The ARC-tag serves as a synthetic ligand for the Antigen-Receptor Complex (ARC) expressed on universal T-cells. In the ACLX-002 system, the adapter protein SPRX002 binds to CD123 on tumor cells via its targeting domain and presents the ARC-tag to ARC-T cells. The high-affinity binding between the ARC receptor and the ARC-tag creates a bridge (tricomplex) that triggers T-cell activation, expansion, and cytotoxic activity against the CD123-expressing cancer cells.