A novel fully human single-domain antibody (sdAb) based CAR-T targeting B7-H3 exerts cytotoxicity against human cancer cell lines in vitro

B7-H3 is a B7 family immune co-stimulatory molecule that is highly expressed on the surface of many tumors but shows low or undetectable expression in normal tissues, making it a promising target for cancer therapy. To date, several B7-H3-targeted CAR-T therapies based on conventional antibody scFv formats have shown progress in tumor treatment; however, no such products have yet received regulatory approval. Single-domain antibodies (sdAbs), which consist solely of the heavy-chain variable domain, have demonstrated favorable properties across multiple therapeutic modalities. In this study, we screened a fully‑human phage‑display library and identified a B7‑H3‑targeting sdAb, SIPI20006, which exhibited high specificity toward both the 4Ig and 2Ig isoforms of B7‑H3. SIPI20006‑engineered CAR‑T cells exerted antigen‑specific cytotoxicity against B7‑H3‑positive SKOV3 and A172 tumor cells.