UCLA researchers use stem cells to engineer ‘killer’ T cells targeting HIV
Posted Dec 15 2009 8:16am
[NOTE: When news breaks in the world of HIV/AIDS science and treatment, we ask our resident HIV Health Librarian, Eric Brus, to review the coverage, verify its claims, and provide additional context relevant to the people we serve. The following is Eric’s review of the recent headlines regarding a stem cell approach to destroying HIV in the body.]
Last week, UCLA’s AIDS Institute reported that they had successfully used human blood stem cells to engineer CD8 cytotoxic T-lymphocytes (CTLs) capable of targeting and killing HIV-infected cells. This novel approach for fighting HIV is still in the very early stages of research. However, UCLA scientists are hopeful that their efforts will someday lead to new immune-based strategies for fighting HIV, other chronic viral illnesses, and possibly cancers.
The UCLA team drew on previous research showing that some long-term nonprogressors have unusually high numbers of CTLs that specifically attack HIV-infected cells. Long-term nonprogressors are the relatively small number of HIV-infected persons whose immune systems are able to control HIV infection for long periods of time without treatment. Unfortunately, the vast majority of HIV-infected persons lack sufficient HIV-specific CTLs to fight HIV infection effectively. Earlier attempts had been made to boost the number of HIV-fighting CTLs by extracting them from a person, growing additional CTLs outside the body, and then reinfusing these CTLs. This approach failed, however, because these CTLs were short-lived and not fully functional.
In the current research, UCLA scientists isolated HIV-targeting CTLs from the blood of an HIV-infected person. They identified and cloned molecules known as the T-cell receptors from the CTLs. These receptors are involved in the process whereby CTLs recognize and kill HIV-infected cells. The UCLA team used the cloned receptors to engineer human stem cells capable of fighting HIV. Next, these engineered stem cells were placed into human thymus tissue that had been implanted into mice. This allowed the researchers to study how the engineered stem cells functioned in a living organism.
The UCLA team found that the engineered stem cells grew into a large population of long-lived, well-functioning HIV-fighting CTLs–a promising result. According to UCLA researcher Dr. Jerome Zack, the next step will be to see whether this approach can be used to engineer HIV-fighting CTLs that can thrive and reproduce in humans.
Developing this approach into a workable HIV treatment presents some important research challenges, according to the UCLA team. Their early research indicates that the cloning and growth of CTLs will have to be tailored to each individual HIV patient, which could make the approach costly and time-consuming. In addition, HIV has the capacity to mutate in ways that allow it to evade some HIV-fighting CTLs. As a result, it may be necessary to isolate and grow a variety of HIV-fighting CTLs from each patient to provide lasting control of HIV infection, even if the virus mutates.