BL22

BL22, also called CAT-3888 or GCR-3888, is an immunotoxin which attaches to and, upon internalization, kills B cells. It has completed a Phase I clinical (human) trial and is currently in a Phase II clinical trial for the treatment of hairy cell leukemia at a Phase I clinical trial for pediatric acute lymphoblastic leukemia and non-Hodgkin's lymphoma [http://clinicaltrials.gov/ct/show/NCT00077493?order=2] at the NIH in the U.S. It may be useful against any B cell leukemia or lymphoma.

Technically, BL22 is an anti-CD22 immunotoxin fusion protein between a murine anti-CD22 disulfide-linked Fv (dsFv) antibody fragment and an edited copy of bacterial Pseudomonas exotoxin PE38. The toxin is activated intracellularly, by the low pH of the lysosome into which the entire protein was internalized via the CD22 receptor. The toxin kills the targeted cell through ribosome inactivation. [http://www.biospace.com/news_print.aspx?NewsEntityId=1132]

BL22 is very similar to the newer HA22, which changes one amino acid in the antibody fragment to increase the binding affinity for the target molecule. Both of these proteins are designed to bind to the CD22 receptor on the surface of B cells.

Business History

BL22 was initially designed and produced at the U.S. National Cancer Institute, one of the agencies which make up the NIH. Early development of BL22 was funded by California biotech Genencor. [http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/11-01-2005/0004204747&EDATE=] The future drug was acquired by Cambridge Antibody Technology at the end of 2005; less than a year later, CAT was purchased by British pharmaceutical company AstraZeneca. [http://www.astrazeneca.com/pressrelease/5266.aspx]