Scientists have been able to genetically engineer the immune cells of twelve HIV positive individuals, allowing them to counter the virus and decrease the amount of infective agents in some of the patients’ bodies, even when antiretroviral drugs are removed from their prescription notes.
Publishing their data and results in the New England Journal of Medicine, the team was assembled from various colleges in the United States, with specialists from the Perelman School of Medicine, University of Pennsylvania, Philadelphia, the Albert Einstein College of Medicine, Bronx, New York, and from Sangamo BioSciences in Richmond, California.
The findings are rather remarkable, with one of the patients, who was off antiretroviral drugs, developing undetectable levels of the pathogen.
What makes this research even more unique is the fact that the techniques used by the research team are a first of its kind: genetic editing in humans.
The work by the American team is catalogued as a Phase 1 Study, typically introducing a compound and performing intensely monitored research on a small trial group, looking into the effects of said drug, or even genes, for example, on the human body.
The scientists looked to modifying the patients naturally occurring T-cells, which are a type of lymphocyte that vary in function. Such functions include cell signaling when encountering a foreign object, virus and cancer elimination, and the capacity to “remember” past infections, which allows a faster and more efficient immune reaction.
The cells in question are known as CD4 T cells, part of the class of lymphocyte (white blood cell) known as helper cells, that typically signal to other immune cells when detecting a pathogen in the body.
HIV often targets white blood cells due to the presence of structures, such as CD4 or CCR5 that typically acts as a cell surface receptor for chemicals, on their surface, using the structure as a co-receptor by which it can enter the cell.
In order to modify these cells, the scientists used the Zinc Finger Nuclease technology, which has been mentioned in a previous article.
These “scissors” allow the CD4 T cells to mimic an extremely rare mutation present in barely one percent of the global human population, known as the CCR5-delta-32 mutation.
By implanting this mutation in the white blood cells, the scientists were able to reduce the expression of these cell surface proteins usually utilised by the virus, creating a cell that blocks out HIV.
The research team used infusions to insert the modified white blood cells into the HIV positive patients, with each treatment consisting of around ten billion cells. Part of the study was to investigate whether this form of treatment is a safe and viable option for human use, which was confirmed by the specialists.
The half-life of these modified cells was estimated to be 48 weeks, however, the decline in these cells was significantly less than that of the normal cells in the HIV positive patients. Importantly, analysis of the gut-associated lymphoid tissue, which is known to hold immune cells and an important area for HIV conditions, showed the presence of the genetically enhanced white blood cells, which the team suggested as signs that they were working normally in the human body.
In addition, the viral load, or amount of HIV in the blood, decreased dramatically in patients who were taken off the traditional antiretroviral therapy for a period of three months.
Although a “cure” is still to be discovered, the results of the study are particularly promising in the treatment of HIV. The innovative Zinc Finger Nuclease technology shows particularly interesting signs for protecting the vulnerable T cells, with further clinical trials looking into large study samples and an increased dose of modified cells being planned, with the hope that this type of treatment can have therapeutic effects.
In what other aspects of medicine would you like to see gene therapy investigated?