But now, scientists at The Scripps Research Institute (TSRI) have discovered a way to make these cells resistant to HIV by tethering HIV-fighting antibodies to them. And experiments show that these resistant cells quickly replace the infected cells—potentially leading to a cure.
“This protection would be long term,” said Dr. Jia Xie, senior staff scientist at TSRI and first author of the study. The team, led by study senior author Dr. Richard Lerner, a Lita Annenberg Hazen Professor of Immunochemistry at TSRI, now plans to collaborate with investigators at City of Hope’s Center for Gene Therapy to further evaluate the safety and efficacy of this potentially groundbreaking new therapy.
“The ultimate goal will be the control of HIV in patients with AIDS without the need for other medications,” said Dr. John A. Zaia, director of the Center for Gene Therapy in the Hematological Malignancy and Stem Cell Transplantation Institute at City of Hope.
The new TSRI 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 receptor and infecting a cell.
Dr. Xie called it the “neighbor effect.” An antibody stuck nearby is more effective than having many antibodies floating throughout the bloodstream.
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.
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 uninfected 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.
Again, their technique worked. The antibodies recognized the CD4 binding site, blocking HIV from getting to the receptor—the researchers ended up with an HIV-resistant population.
Dr. Joseph Alvarnas, director of Value-Based Analytics at City of Hope, explained how the TSRI technique could help patients, who—despite treatment with antiretroviral drugs—still suffer from higher rates of other diseases, such as cancers. “HIV is treatable but not curable—this remains a disease that causes a lot of suffering. That makes the case for why these technologies are so important,” he said.
Source : The Scripps Research Institute