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Monday, November 10, 2008

Genetically Engineered Immune Cells Catch Disguised HIV

Technique may offer new way to treat the infection, researchers say

Reuters

WASHINGTON - Genetically engineered immune cells can spot the AIDS virus even when it tries to disguise itself, offering a potential new way to treat the incurable infection, researchers reported on Sunday.

The killer T-cells, dubbed "assassin" cells, were able to recognize other cells infected by HIV and slow the spread of the virus in lab dishes.

If the approach works in people, it might provide a new route of treating infection with the deadly human immunodeficiency virus, the researchers in the United States and Britain said.

"Billions of these anti-HIV warriors can be generated in two weeks," said Angel Varela-Rohena of the University of Pennsylvania, who helped lead the study.

In a second, unrelated report, researchers testing Dutch biotechnology firm Crucell NV's experimental AIDS vaccine said it prevented infection in six monkeys.

The animals were infected with a monkey version of HIV called SIV, and the vaccine used a virus that is dangerous to use in humans, so it is not ready for human tests.

But, writing in the journal Nature, Dr. Dan Barouch of Beth Israel Deaconess Medical Center and Harvard Medical School in Boston and colleagues said it shows there is still hope for developing a vaccine against AIDS.

The AIDS virus, which infects 33 million people globally, is especially hard to fight. Like all viruses, it hijacks cells in its victims, forcing them to become little viral factories and make more virus.

Escape and evade
HIV is even more insidious, attacking immune system cells called CD4 T cells, which help mount a defense. It can also disguise itself to escape CD8 killer cells, also known as cytotoxic T lymphocytes or CTLs.

"CTLs are crucial for the control of HIV infection. Unfortunately, HIV has an arsenal of mutational and nonmutational strategies that aid it in escaping from the CTL response mounted against it by its host," the researchers wrote in their report, published in the journal Nature Medicine.

One good defense allows HIV to hide a protein called HLA-I-associated antigen.

Varela-Rohena and colleagues took T-cells from an HIV patient and created a genetically engineered version that recognizes this deception.

"It is possible to improve on nature when it comes to preventing HIV CTL escape," they wrote.

Not only could the engineered T-cells see HIV strains that had escaped detection by natural T-cells, "but the engineered T cells responded in a much more vigorous fashion so that far fewer T-cells were required to control infection," Penn's James Riley, who also worked on the study, said in a statement.

"In the face of our engineered assassin cells, the virus will either die or be forced to change its disguises again, weakening itself along the way," added Andy Sewell of Britain's Cardiff University.

Perhaps having to mutate will weaken the virus, the researchers said.

They plan to test the T-cell treatment in HIV patients next year.

"We have managed to engineer a receptor that is able to detect HIV's key fingerprints and is able to clear HIV infection in the laboratory," said Bent Jakobsen, chief scientific officer at Adaptimmune Ltd, a British company launched in July that owns the rights to the technology. "If we can translate those results in the clinic, we could at last have a very powerful therapy on our hands."

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