The BC-821 plasmid is a modification of the design utilized in inodiftagene (formerly BC-819). The concept is similar: deploy cancer-specific gene-regulatory elements to specifically target toxin expression in transduced cancer cells. However, in BC-821 a second promoter has been added from IGF2, coupled to a second copy of DTA.
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 bladder 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.