Scientists are touting a discovery that they think might cure HIV infection. They’ve engineered an antibody that blocks the virus from entering and infecting key immune system cells.
The process, developed at the Scripps Researcher Institute in California, involves tethering an antibody, which fights infection, directly onto T cells, the immune system cells that are targeted by the AIDS virus. Eventually, if enough immune cells become infected and destroyed by HIV, the disease progresses to AIDS, which leads to certain death. The antibodies, however, block the receptor on the T cells that HIV uses to enter and destroy them.
It’s what immunochemist Richard Lerner called a form of “cellular vaccination.” He said the genetic alteration of the T cells with tethered antibodies does not interfere with the immune cells’ ability to fight other pathogens.
Lerner is the senior author of a study describing the work in Proceedings of the National Academy of Sciences.
Experimental HIV vaccines attempt to stimulate an immune response, creating HIV-specific antibodies to attack and destroy infected cells. But Lerner says the concentration of antibodies flowing freely in the bloodstream is too low to reach every infected T cell.
‘Survival of the fittest’
This approach is different, protecting only some healthy T cells.
“You don’t really care about the rest of the body,” Lerner explained. “You would just like to shield those cells from viruses and a virus attack. So that’s the chemical principle. Never mind immunizing the whole body. Just immunize the cells that are the real victims.”
His team added a gene to T cells which instructed them to synthesize antibodies that would bind with the cellular receptor called CD4. That is the doorway to the cell for HIV. Having antibodies hanging on to the cell surface blocks that doorway.
It’s hoped that eventually in humans, these HIV-resistant cells will multiply into the millions, passing on the protective gene, as the unprotected, infected cells die off, eradicating the AIDS virus from the body and affording a long-lasting cure.
At least that’s what experiments in the laboratory suggested when both genetically engineered and unprotected human T cells were exposed to HIV.
Lerner said the engineered T cells would be introduced into a patient’s bone marrow, which would produce protective cells en masse.
“We hope to, after securing their safety and so on and so forth, in a patient with HIV, [the engineered cells] can harm their [infected] cells with [the] resistance of ours, and … hopefully the good cells will be selected over the bad cells. And that will be the end of HIV in that patient,” Lerner said.
It’s an approach that Lerner calls a Darwinian “survival of the fittest.”
Scripps investigators are working with City of Hope, an independent research and comprehensive cancer treatment center in Duarte, California, that has a lot of experience with bone marrow transplantation. The center will carry out clinical trials of the engineered, HIV-resistant T cells with an eye toward advancing what scientists hope will be a cure for AIDS.
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