Researchers at Albert Einstein College of Medicine made a quantum leap in the treatment of HIV by transformming the genetically reprogrammed immune cells to fight HIV.
A subgroup of immune cells known as CD8 cytotoxic T lymphocytes, or CTLs, recognize cells infected with HIV and kill them before they become HIV-producing factories. This CTL activity initially keeps the infection in check.
AdvertisementHowever, CTLs may not bind tightly enough to the infected cells or because HIV mutates so rapidly, the virus subdues the immune system, thus boosting the virus in the absence of drug therapy and resulting in AIDS.
"Certain of the CTLs of elite controllers may be genetically equipped to bind tightly to HIV-infected cells and destroy them and thereby suppress the infection indefinitely," said Dr. Harris Goldstein, senior author of the study and Director of the Einstein/Montefiore Centre for AIDS Research.
"Our idea was first to identify the elite controllers' "super" CTLs and to isolate the genes that enable these cells to bind tightly to HIV-infected cells and kill them efficiently; then we would transfer these genes into CTLs that do not recognize HIV-infected cells and convert them into potent killers of those cells," he added.
CTL's T-cell receptor, which is unique for each CTL has two "chains," alpha and beta, the researchers isolated the genes that code for each of the two "chains" from the potent HIV-specific CTL.
The genes were combined and packaged inside a special type of virus, called a lentivirus. The lentiviruses then inserted these genes into the chromosomes of naive CTLs obtained from a naive donor's (people not infected with HIV) blood and reprogrammed them into potent HIV-specific CTLs.
During the study, the researchers injected mice with both HIV-infected human cells and with reprogrammed naive CTLs into which the HIV-recognizing T-cell receptor genes had been inserted using the lentiviral delivery system.
The findings revealed that after one week the infected cells had virtually been eliminated.
"We demonstrated that these genetically reprogrammed CTLs have very strong activity in terms of killing HIV-infected cells in both test tubes and an animal model," said Goldstein
Researchers believe that the novel strategy could lead to an entirely new approach for combating AIDS and other viral diseases.
The findings appear in the March issue of the Journal of Virology.