Definition

An immunotherapeutic combination agent composed of antigen receptor complex T cells (ARC-T cells) which contain a proprietary binding domain specific for a universal TAG instead of a single chain variable fragment (scFv) binding domain, and a tumor-targeting antigen protein, soluble protein antigen-receptor X-linker (sparX) protein, containing a TAG moiety fused to two B-cell maturation antigen (BCMA; tumor necrosis factor receptor superfamily member 17; TNFRSF17) binding domains, with potential antineoplastic activities. Upon administration of the anti-BCMA sparX protein plus BCMA-directed ARC T-cells CART-ddBCMA, the sparX protein, with its two BCMA binding domains, specifically targets and binds to two BCMA expressed on tumor cells. In turn, the ARC-T cells, with their anti-TAG domain, target and bind to the TAG domain on the sparX protein. This directly links the ARC-T cells to the BCMA-expressing tumor cells, through the ARC-T cell- sparX -tumor cell complex formation, thereby causing direct tumor cell killing. BCMA, a tumor-associated antigen (TAA), is found on the surfaces of plasma cells and is overexpressed on a variety of tumor cell types. Compared to anti-BCMA CAR-T cells, CART-ddBCMA, containing ARC-T cells that are re-programmed in vivo by the TAG sparX protein, shows enhanced efficiency and an improved safety profile. As ARC-T activity is dependent on the sparX dose administered, the rate of tumor cell killing, and related toxicities are also dependent on the sparX dose administered.