Cytomegalovirus, or CMV, is a moderately infectious herpesgroup virus. It is rarely associated with symptoms in healthy individuals, but like other members of the herpes family it remains in the body, contained by the normal immune system, from infection until death. It is found all over the world, and typically 75-80% of a country’s population are CMV positive by the age of 40. It is the most common virus passed between mother and developing child in utero, and after birth can be contracted from any exchange of body fluids.

CMV, although normally unnoticed by the carrier, can cause serious health problems in immunocompromised patients. CMV pneumonia is one of the leading causes of morbidity and mortality among immunosuppressed patients after bone marrow transplant (BMT) procedures.

Before a BMT can be carried out, the patient’s bone marrow is pretty pretty much anihilated with heavy chemotherapy. This has the unfortunate consequence of effectively destroying the patient’s entire immune system. When the donor bone marrow is transplanted, it takes it several weeks to begin building the recipient’s immune cell numbers back to normal levels. During this period, the recipient is kept in relative isolation and great care is taken to prevent infection with any pathogens from medical staff and so forth. However, if the patient is CMV positive, they already have a virus capable of causing serious illness in their body.

During the period of rebuilding the recipient’s immune system, all specific immune responses have to be redeveloped from scratch. This of course includes the specific immune cells that have been keeping the recipient’s CMV infection under control. The virus has several weeks in which it can multiply unchecked, causing severe and often fatal illness. Anti-viral drugs are used in life-threatening cases, but tend to be fairly ineffective.

With treatment of post-BMT CMV illness limited, research has concentrated on preventing it in the first place. The obvious approach is to reduce, or even eliminate entirely the period of low or zero specific immune response to the virus. To do this, the recipient needs to recover a fairly high number of CMV-specific immune cells, particularly T-cells, very rapidly after their transplant. The recipient’s own CMV-specific T-cells have been wiped out, so donor cells need to be provided.

Even if the donor is CMV positive, however, standard blood won’t provide enough T-cells to control the virus in the recipient. Besides, 20-25% of donors are CMV negative, and have no T-cells specific for the virus.

Fortunately, the situation can be improved with advanced cell culture techniques. T-cells from the donor can be isolated from a small blood sample and grown in vitro. At the same time, a culture of a generic lymphocyte cell line is transfected with CMV. The transfected cell line is irradiated to stop further division of the culture, and is introduced to the T-cells. The T-cells respond as they would in vivo, becoming increasingly specific for the CMV antibodies they find in their culture. In effect, the T-cells are ‘trained’ to recognise cells infected with the virus. After this training process, up to 70-80% of a culture of non-specific T-cells will have become CMV specific.

When these cells are transfused into the recipient, they will function as the normal immune system would, keeping the virus under control. The cells live for a few weeks in the recipient’s bloodstream, before dying as normal lymphocytes do. By that stage, the recipient will hopefully be producing enough immune cells of their own to stay healthy.

Early limited patient trials of this technique are being carried out at Westmead Hospital, Sydney, Australia.

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