The success of rituximab, Bexxar, and Zevalin has spawned an entire industry of monoclonal antibody research in the treatment of follicular lymphoma and related diseases. Some of the most novel of these follow Bexxar and Zevalin in combining the antibody with a useful pharmaceutical payload.
How Inotuzumab Works: Inotuzumab is an anti-CD22 antibody, attacking a different protein than the more established drugs (which mostly target CD20). Inotuzumab itself is a humanized antibody, which carries a calicheamicin antibiotic. Once the antibody binds to the cell, the antibiotic is released into the cell and kills it. Calicheamicin is one of the most powerful anti-cancer agents in our experimental arsenal today; what is lacking, outside of drug candidates like this one, is an effective way to deliver it to the target.
Like rituximab, inotuzumab targets only B cells in the immune system, meaning it can be delivered in potent amounts against cancer without the systemic side effects of older chemotherapy drugs.
Drug Status: Currently in trials.
Side Effects: Almost all patients have reduced white blood cell counts. Three-quarters also suffer from anorexia and nausea.
Response Rates: In an impressive Japanese study reported in early 2010, 13 follicular lymphoma patients who had failed previous rituximab-based therapies were given IV inotozumab daily for 28 days. Despite the fact this population was heavily pre-treated, there was an 85% response rate, including seven complete remissions (54%).
Published Studies
Michinori Ogura et al. "Phase I Study of Inotuzumab Ozogamicin (CMC-544)." Cancer Science (2010).
Calicheamicin, also known as Calichemicin γ1, is an potent enediyne antitumor antibiotics derived from the bacterium Micromonospora echinospora. Calicheamicin targets DNA and cause strand scission. Calicheamicin
ReplyDelete