'Assassin cells' to treat HIV

Behind the Headlines

Tuesday November 11 2008

The Guardian reports that “assassin cell” therapy could be used to treat people with HIV, using specially enhanced white blood cells to target the virus.

The technology takes advantage of the ability of certain people’s immune systems to keep up with the mutations of the virus, with researchers enhancing the ability of certain white blood cells, called T-cells, to recognise and attack cells infected with HIV.

To date the technology has only been assessed in the laboratory and it remains to be seen whether it might prove effective within the human body. The process also relies on very specific parts of T-cells, that may vary between ethnic groups. Much more research will be needed to see if this technology can develop viable treatments for thousands of people living with HIV in the UK, and the millions more around the globe.

Where did the story come from?

Dr Angel Varela-Rohena and colleagues from the University of Pennsylvania School of Medicine, Immunocore Ltd, the University of Oxford, Cardiff University School of Medicine and Adaptimmune Ltd. The study was published in the peer-reviewed medical journal Nature Medicine.


What kind of scientific study was this?

This was a study concerned with the use of modified ‘killerT-cells’ - a particular type of white blood cell in the human body, on HIV infection in the laboratory’


There are different types of T-cells, some of which are a target for the HIV virus. When the virus infects these particular T-cells it takes over their systems, using them to replicate more virus particles. In turn other types of T-cells, the cytotoxic (or killer) T-cells, are responsible for recognising these infected cells and killing them off.

The ‘success’ of an HIV infection can be attributed in part to the capacity of the virus to evade the defences of the human immune system, such as killer T-cells. Evading the body’s defences is achieved through rapid and regular mutations in the HIV virus. When an ‘escape’ mutation occurs it affects the viral proteins that remain on the outside of infected cells. These proteins normally alert the body’s killer T-cells to the presence of an invader.

When these proteins, or receptors, are removed or disguised, the HIV replicating in the cells is therefore able to escape detection. It seems that certain humans are able to fight the infection, as their bodies can recognise these external proteins, and have better control of their disease and increased life expectancy.

In this study, the researchers were interested in exploring whether they could enhance the properties of the killer T-cells to recognise disguised HIV-infected cells.

Researchers removed killer T-cells from an HIV patient whose immune system appeared to be able to recognise those HIV viruses that were escaping detection. They cultured these cells and mutated them to select those versions that had the greatest affinity for a protein, called SL9, that appears on the surface of cells that HIV infects.

They investigated the properties of these cultured T-cells and observed their response to various concentrations of SL9 on cells in the laboratory. To investigate the effects of these immune cells on HIV infection, researchers infected other types of T-cell with HIV and then observed whether these enhanced killer T-cells would have an effect on the spread of HIV in the culture.


What were the results of the study?

The researchers found that their mutated T-cells had a high affinity for the SL9 protein, which is found on cells infected with HIV. They say that the study suggests their mutated cells would ‘successfully target HIV-infected cells’, based on the ability to bind to the SL9 protein demonstrated in the laboratory. However, they could not investigate this as preparing the HIV virus for testing outside of the body leads the T-cells to respond less effectively.


When investigating the effect of the T-cells on HIV infected cells in laboratory culture, the researchers found that they were able to limit the spread of HIV better than ordinary (non-enhanced) killer T-cells.

What interpretations did the researchers draw from these results?

The researchers conclude that the properties of these enhanced killer T-cells make them an attractive potential therapy for HIV.


What does the NHS Knowledge Service make of this study?

This laboratory study has explored a potentially new avenue to treat HIV in humans, based on the idea that a patient’s own T-cells are mutated (enhanced) to be able to recognise HIV better and thereby target them for destruction.


The researchers hope that increasing the capacity of the body to detect HIV will either kill off the virus or at least weaken it as it tries to mutate Weakening the virus may slow its progress and reduce its ability to transmit within the population.

So far the studies have only been carried out in a laboratory, and future human testing is important. According to The Guardian a human study will begin next summer through the University of Pennsylvania. Until then it is unclear whether this technology will provide a potential treatment option for people living with HIV, or an effective method to reduce the spread of the virus.

As suggested by the news report, the technology relies on a very specific part of the T-cells which may vary across individuals and different ethnic groups.

While this study opens an exciting new avenue in HIV treatment, it remains unclear whether this preliminary research will lead to development of a treatment for HIV.


SIr Muir Gray adds...

This looks promising, but it will be dificult to develop.


Analysis by Bazian

Edited by NHS Choices

Links to the headlines

'Assassin cell' therapy to tackle HIV. The Guardian, November 10 2008

'Assassin' cells home in on HIV. BBC online, November 10 2008

Links to the science

Varela-Rohena A, Molloy PE, Dunn SM et al. Control of HIV-1 immune escape by CD8 T cells expressing enhanced T-cell receptor. Nat Med, 2008 Nov 09 [Advanced online publication]


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