 |
|||
 |
 |
 |
|
PRO 140
PRO 140 is a humanized monoclonal antibody developed by Progenics' scientists, designed to block HIV infection by inhibiting the virus' ability to bind to and enter immune system cells. As a monoclonal antibody PRO 140 is not expected to be metabolized by the liver and, as such, has the potential for a better tolerability profile than many approved therapies for HIV infection. Unlike small-molecule CCR5 antagonists, PRO 140 inhibits HIV entry at concentrations that in vitro do not appear to block CCR5's natural activity of directing the migration of immune cells towards sites of inflammation in the body.
PRO 140 was given "Fast Track" designation by FDA, a formal process which facilitates development and expedites regulatory review of drugs intended to address unmet medical needs for serious or life-threatening conditions.
How PRO 140 works
PRO 140 prevents HIV from entering healthy immune system cells by binding to a distinct site on the cellular co-receptor CCR5; one of two receptors required for HIV entry into susceptible cells -- the other is the T-Cell CD4. CCR5's role in HIV infection was characterized by Progenics and its collaborators in 1996.1 (Some strains of HIV use the CXCR4 co-receptor as a portal of entry either exclusively or alternatively with CCR5 and are therefore not inhibited by PRO 140).
Through its surface glycoprotein 120 ("GP120"), HIV first binds to CD4, and
then binds to either the CCR5 or CXCR4 co-receptor, thus enabling conformational
changes that permit fusion of the virus with the cell membrane, and facilitate
entry of the viral genetic information into the cell and subsequent viral
replication. By binding to CCR5 first, PRO 140 blocks HIV from binding to CCR5
and fusing with the cell membrane, thereby inhibiting the viral replication
process.
1 Dragic, et al. Nature. 381, 667-673
(1996)