293c3-sdie

293C3-SDIE is a chimerized, Fc-optimized monoclonal antibody targeting CD133 (prominin-1), a cell surface glycoprotein expressed on certain cancer stem cells and cancer cells, including colorectal cancer (CRC) and B-cell acute lymphoblastic leukemia (B-ALL). The antibody’s Fc region has been engineered (with the amino acid exchanges S239D/I332E) to enhance affinity for the Fc receptor CD16 (FcγRIIIa) on natural killer (NK) cells, thereby promoting antibody-dependent cellular cytotoxicity (ADCC) against CD133-positive tumor cells[1][2]. In preclinical studies, 293C3-SDIE demonstrated potent induction of NK cell activation, degranulation, interferon-γ secretion, and tumor cell lysis in vitro, with efficacy correlating to CD133 antigen density on target cells[1][2]. It showed no direct effect on tumor cell viability in the absence of immune effector cells, indicating that its anti-tumor activity is mediated through immune cell engagement rather than direct cytotoxicity[1]. The antibody is considered a “ready-to-use,” off-the-shelf product, contrasting with more complex immunotherapies like CAR-T cells[1]. Primary indications under investigation include CRC and B-ALL, particularly in patient subgroups with high CD133 expression and in cases where other targeted therapies (e.g., anti-EGFR antibodies, checkpoint inhibitors) have limited efficacy[1][2]. There is also evidence suggesting potential utility in MLL-AF4-rearranged B-ALL, a high-risk subset[2]. The preclinical safety profile suggests minimal toxicity to healthy hematopoietic progenitor cells, likely due to lower CD133 expression compared to malignant cells[2]. Clinical development is warranted to further evaluate efficacy and safety in humans.