Aplitabart is an IgM antibody targeting death receptor 5 (DR5) and is being developed for the treatment of patients with colorectal cancer.
The potential of multimeric binding
Death receptor 5 is a member of the tumor necrosis factor receptor superfamily (TNFrSF) and is often expressed on the surface of cancer cells. Strong activation of the DR5 pathway requires multiple receptors to be cross-linked simultaneously by an antibody or other binding agent to create an apoptotic death signal to the cell. Unlike traditional IgG antibodies, Aplitabart has 10 binding units, giving it an advantage to cross-link multiple DR5 receptors at once, sending a stronger signal to cause cancer cell death.
In addition, the unique natural structure of an IgM antibody may allow us to improve the safety profile of DR5 binding agents by controlling the clustering of DR5 on healthy cells and timing of the apoptotic signal, thereby reducing harmful side effects like liver damage. In our studies, DR5 IgM antibodies have significantly enhanced in vitro killing potency on cancer cells, as compared to IgG antibodies with the same binding units.
Aplitabart is currently being evaluated in randomized combination trials for the treatment of colorectal cancer.