CD123-specific adapter SPRX002

A soluble protein antigen-receptor X-linker (sparX) protein containing a CD123 tumor-associated antigen (TAA) binding-domain and a TAG domain, which contains a fragment of human alpha fetoprotein (AFP), with binding ability to CD123-specific tumor cells and universal CAR-modified T cells (antigen-receptor complex-T cells; ARC-T cells), respectively. Upon administration, the CD123-specific adapter SPRX002 targets and binds, with its anti-CD123 binding domain, to CD123-expressing tumor cells and, with its TAG region, targets and binds to the anti-TAG binding domain on the ARC-T-cells. When ARC-T cells bind to the TAG domain of SPRX002 and SPRX002 is bound to CD123-expressing cancer cells, the tricomplex formation leads to T-cell activation, expansion and killing of CD123-expressing cancer cells. The combination of SPRX002 with ARC-T cells is called ACLX002. Since the dose of SPRX002 can be adjusted, it allows for the controllability and adaptability of the ARC-T cells and reduces its potential toxicity .CD123 is normally expressed on committed blood progenitor cells in the bone marrow; its overexpression is associated with both increased leukemic cell proliferation and aggressiveness.