Word: ibalizumab
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Dates: during 2010-2010
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...initial reaction was, Are you crazy?" recalls Sandy Vasan, a researcher at ADARC who, along with Ho and Huang, is now heading the ibalizumab studies. A clinician who sees patients, Vasan says, "It's really scary to want to put an antibody on CD4. You need CD4." (See "The Year in Health 2009: From...
What the ADARC scientists are struggling to achieve is a thorough understanding of how ibalizumab operates and how they can control those machinations. The CD4 cell is a bit like an immunological sentinel, endowed with the ability to recognize snippets of various pathogens, from common influenza to HIV, and mark them for destruction by other cells. Once attached to a CD4, HIV begins an intricate series of steps to gain entry into the cell. Ibalizumab is able to disrupt this intricate molecular choreography by binding to the CD4 and serving as an immunological snare. With the antibody stuck...
...believes ibalizumab is more agile than that. CD4, it turns out, is like a marina with several docks; HIV berths in one, and ibalizumab in another, leaving the cell free to fight other pathogens. "If CD4's binding site to HIV is with its nose, then this antibody is binding to the back of CD4's neck," Ho says. That means the cell's ability to function as a pathogen troller is not impaired by being coupled to ibalizumab. "There is a solid scientific rationale for what they are attempting to do," says Harvard's Walker...
...working with monkeys to test whether ibalizumab can head off infection not just with the notoriously weaker lab strains of HIV but also but with naturally circulating strains as well. The idea is to hit the antibody with the most potent HIV around, so if the strategy doesn't work, Ho can shut down the project, before it gets too far along...
...hoping it won't come to that. He is not under any illusion that a successful antibody-based treatment will have the sweeping effect of the polio or measles or smallpox vaccines - essentially wiping out the diseases in treated populations. Instead, an ibalizumab-based therapy will be just one of many weapons against HIV, albeit a very powerful one. "At our first meeting on this, I said I have a strategy that I feel will work," Ho recalls. "It was truly my gut feeling...