Scientists at The Scripps Research Institute (TSRI) have discovered a way of creating HIV- resistant cells by using antibodies to block HIV directly on the cell surface. Interestingly, in lab experiments, the resistant cells largely replaced the susceptible cells, potentially leading to long-term HIV protection.
Study senior author Dr. Richard Lerner (Photo by Kevin Fung)
The new technique, which researchers referred to as “a form of cellular vaccination,” has an advantage over other therapies in that the antibodies are expressed by the cell and dock on the cell surface rather than float freely throughout the bloodstream. This allows the antibodies to block the specific interaction between HIV and CD4, the primary cell receptor for entry of the virus. However, the antibodies do not block CD4 from performing normal cellular activities.
Scientists initially used the rhinovirus as a model, which is responsible for many cases of the common cold. They used a lentiviral vector to deliver a new gene to cultured human cells. The new gene instructed cells to synthesize antibodies that bind with the human cell receptor that rhinovirus needs.
In a Darwinian “survival of the fittest” lab dish, cells without antibody protection died off, leaving protected cells to survive and multiply, passing on the protective gene to new cells.
Researchers then tried the technique against HIV. The scientists aimed to protect immune cells normally killed by HIV. Using the same technique to discover antibodies that would specifically block the HIV-CD4 interaction, scientists engineered immune cells to express the antibody gene. The researchers found that even after attempted infections in a petri dish, the cells were resistant to HIV.
Dr. Marcella Flores, associate director of research for amfAR
The researchers, led by study senior author Dr. Richard Lerner, Lita Annenberg Hazen Professor of Immunochemistry at TSRI, plan to collaborate with investigators at City of Hope’s Center for Gene Therapy in Los Angeles to evaluate the new therapy before testing in patients. City of Hope currently has active clinical trials of using gene therapy and blood stem cell transplantation to cure HIV.
“The ultimate goal will be the control of HIV in patients with AIDS without the need for other medications,” said Dr. John Zaia, director of the Center for Gene Therapy in the Hematological Malignancy and Stem Cell Transplantation Institute at City of Hope.
Commenting on the study for the San Diego Union-Tribune, amfAR’s associate director of research Dr. Marcella Flores said the "dock and block" technique described by these researchers holds promise as an alternative to stem cell transplantation. But she said more study is required before patient trials can commence.
The findings were published April 12 in Proceedings of the National Academy of Sciences.