Immunochemical engineering of cell surfaces to generate virus resistance

Immunochemical engineering of cell surfaces to generate virus resistance
 

Scientists have found a way to tether HIV-fighting antibodies to immune cells, creating a cell population resistant to the virus. Their experiments under lab conditions show that these resistant cells can quickly replace diseased cells, potentially curing the disease in a person with HIV.

"This protection would be long term," said first author of the study published in the journal Proceedings of the National Academy of Sciences. The researchers plan to evaluate this new therapy in efficacy and safety tests, as required by federal regulations, prior to testing in patients.

The new technique offers a significant advantage over therapies where antibodies float freely in the bloodstream at a relatively low concentration. Instead, antibodies in the new study hang on to a cell's surface, blocking HIV from accessing a crucial cell receptor and spreading infection.

An antibody stuck nearby is more effective than having many antibodies floating throughout the bloodstream. "You don't need to have so many molecules on one cell to be effective," author said.

Before testing their system against HIV, the scientists used rhinovirus (responsible for many cases of the common cold) as a model. They used a vector called lentivirus to deliver a new gene to cultured human cells. This gene instructed cells to synthesize antibodies that bind with the human cell receptor (ICAM-1) that rhinovirus needs. With the antibodies monopolizing that site, the virus cannot enter the cell to spread infection.

Because the delivery system can't reach exactly 100 percent of cells, the finished product was a mix of engineered and unengineered cells. The researchers then added rhinovirus to these cell populations and waited to see what would happen.

The vast majority of cells died in about two days. In dishes with only unengineered cells, the population never recovered. There was an initial die-off in the mixed engineered/unengineered populations, too, but their numbers quickly bounced back. After 125 hours, these cell populations were back up to around the same levels as cells in an undiseased control group.

In essence, the researchers had forced the cells to compete in Darwinian, "survival-of-the-fittest" selection in a lab dish. Cells without antibody protection died off, leaving protected cells to survive and multiply, passing on the protective gene to new cells.

This success led the researchers to test the same technique against HIV. To infect a person, all strains of HIV need to bind with a cell surface receptor called CD4. So the scientists tested antibodies that could potentially protect this receptor on the very immune cells normally killed by HIV..

Again, their technique worked. After introducing cells to the virus, the researchers ended up with an HIV-resistant population. The antibodies recognized the CD4 binding site, blocking HIV from getting to the receptor.

The scientists further confirmed that these tethered antibodies blocked HIV more effectively than free-floating, soluble antibodies in experiments.

http://www.scripps.edu/news/press/2017/20170410lerner.html
http://www.pnas.org/content/early/2017/04/05/1702764114.abstract?sid=3de594eb-0f12-49b9-b352-da4a150f1301

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