Like BC-819, BC-821’s active sequence is based on two core elements, a promoter and subsequent DTA-coding sequence. However, BC-821 harbor a dual DTA expression system, driven by two distinct core promoters: the H19 promoter and the IGF2-P4 promoter segment.
The IGF2 protein is a member of the “insulin-like growth factor” family that is involved in cell proliferation and differentiation. Similar to H19, the IGF2-P4 oncofetal promoter is functional during two stages in life: embryogenesis and tumor development. Increased expression of IGF2 is frequently seen in a variety of human tumors, including in hepatocellular carcinoma, breast cancer, ovarian cancer and prostate cancer.
BC-821 harnesses the cancer-specific expression patterns of both H19 and IGF2 transcript by using their regulatory elements as cancer-dependent switches for activation of Diphtheria Toxin A.
The use of a dual-DTA expression system which depends on two different promoters has two main advantages: Not only does it provide enhanced cell-killing potential, but also increases the chance that at least one of the promoters will be active in any given tumor, thus increasing the number of tumors responding to BC-821.
BC-821 has been shown to inhibit different cancer cells in tissue-culture experiments (in vitro) and to repress tumor growth in animal models (in vivo). In addition, promising preliminary data shows that BC-821 inhibits very aggressive types of cancers and their metastases when administered intravenously with the transfection reagent polyethylenimine (PEI).