Anti-HIV drugs have prolonged millions of lives, but they have not eliminated the virus from person. Indeed, HIV integrates its genetic material in the chromosomes of certain white blood cells, helping him to escape the attention of the immune system. Two new studies show that artificial antibodies could "redirect" the immune response to these latently infected cells and help drain the HIV reservoirs in the body. But this creative strategy also carries risks.
"The reason is sound, and data are exciting, but we need to move cautiously," said Steven Deeks, a clinical HIV / AIDS at the University of California, San Francisco (UCSF) , which tests the healing strategies. "There's really no room for error."
Several previous studies have investigated whether drugs can shock the cells that are infected with latent HIV to make new virus, setting them up for the kill by the natural immune response. But this new work ups the ante by developing so-called bispecific antibodies that both promise to reverse the lag and do the job of raking. "the dual activity makes this interesting new approach," said Sharon Lewin, a researcher cure HIV who heads the Peter Doherty Institute for Infection and Immunity in Melbourne, Australia. "It's exciting."
The two new documents that appear only online to date, mainly involving experiments test tubes. One, described in Nature Communications today ' hui, was conducted by a team from the vaccine research Center at the US National Institute of allergy and infectious diseases (NIAID) in Bethesda, Maryland. the second study was published last month in the Journal of Clinical Investigation ( JCI ) and involved a collaboration between three universities and a biotechnology company.
both groups artificial versions designed antibodies, the molecules form Y performed by the immune system to target pathogens. In natural antibodies, the two "arms" of the Y enclose the same target. However, the antibody arm bispecific each capture a unique protein. In this case, the two teams their antibodies designed to hug an HIV protein and CD3, a receptor present on the surface of white blood cells.
The bispecific antibodies focus on CD3 receptor for two reasons. The first is that the HIV hides within the DNA of white blood cells or T lymphocytes, which have CD3 receptors. The other is that a second type of CD3-studded lymphocytes cells known as killer T name destroys cells infected with HIV.
The bispecific antibody binds to CD3 first on cells harboring latent HIV. This prompts the cells to divide, a process of "activation" that awakens the virus of sleep. new proteins by HIV are then produced that migrate to the cell surface.
However, the bispecific antibody captures a killer T cell that has a CD3 receptor and with its second arm, is a newly activated cell that HIV proteins on its surface. Bring the killer T cell near the infected cell effectively shoves prey in the lion's mouth. "The molecule works the way you want to hope that it would be in several trials," said John Mascola, director of the NIAID Vaccine Research Center and leader of the group reporting of Nature Communications study.
But no team has yet shown that their bispecific antibodies can effectively reduce HIV reservoirs in monkeys, which are commonly used to study the AIDS virus. These studies are ongoing, and it will take at least a year before either team tests concepts in people infected with HIV. David Margolis, a virologist at the University of North Carolina, Chapel Hill, and co-author of the study JCI , said drain a reservoir ultimately may require combination with bispecific antibodies other reversing latency approaches and immune system stimulators such as HIV vaccines.
Deeks ofUCSF warns that anti-CD3 antibodies can cause too much activation of T cells, leading to a massive inflammatory reaction that damages organs and can even cause death. Indeed, in a 1999 study of anti-CD3 antibodies used for purging the tanks of three people infected with HIV, severe side effects, including kidney failure and seizures surface quickly. But the anti-CD3 antibody in the previous study were the two arms, Mascola ratings, which leads to the activation much more than the single arm in the new bispecific antibodies. It also emphasizes that two bispecific antibodies cancer on both the market have anti-CD3 arms. "The key is to find the right balance between activation and toxicity CD3" said Mascola. "That's the real challenge here."
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