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BIO Magazine - Just five patients but gene therapy leukaemia trial yields positive results Δεκέμβριος 2015
Δεκέμβριος 2015 No38

BIO News

Just five patients but gene therapy leukaemia trial yields positive results
Just five patients but gene therapy leukaemia trial yields positive results

Early results of an experimental gene therapy against an aggressive form of leukaemia have been hailed by researchers as showing 'life-saving potential'.

The study, published last week in the journal Translational Medicine, focussed on the treatment of patients with acute lymphoblastic leukaemia (ALL) - an aggressive, fast-growing cancer of a subset of white blood cells known as 'B cells'.

In the trial, five adult patients' immune cells were removed, genetically modifiedand reinserted back into their bodies to target the tumour. As a result of this experimental treatment, all of the patients' tumours were seen to have significantly shrunk and their cancer sent into remission, demonstrating the therapeutic potential of such 'immunotherapies' in people with cancer.

The team harnessed the normal functioning of a type of immune cell called T cells to achieve this effect. T cells protect the body by fighting infection from certainviruses and cancers. They detect molecules studded on the outside of these infectious agents to 'home in' on them, secreting chemicals called cytokines to destroy the intruders, and so rid the body of infection.

In normal functioning, T cells will only respond to agents displaying these specific molecules, explaining why they do not attack all cancer or viruses, or indeed the body's own cells. However, by modifying the genetics of these cells, Dr Michel Sadelain of Memorial Sloan-Kettering Cancer Center, USA and his team re-trained their patients' T cells to target any cells expressing one particular molecule, called CD19. As CD19 is expressed by leukaemia cells, the modified T cells target and kill them, clearing the leukaemia from the body in the process.

'The T cells are living drugs', Dr Sadelain explained. 'They see the CD19, they kill the cancer cells, and they persist in the body'.

Despite being in the earliest stages of development, these results offer hope for the future treatment of patients with ALL. When, as is most common, ALL occurs in children prognosis is good, with current treatments capable of curing an estimated 80-90 percent of cases. However, this efficacy drops dramatically to below 30 percent when the disease is seen in adults, leading to what Dr Sadelain describes as 'a dismal prognosis'.

The results of this study show that, in such cases, cancers could be driven quickly into remission, crucially allowing patients to become eligible for bone marrow transplants and therefore dramatically improving their prognosis.

The therapy is, however, not without side-effects. Following treatment, two of the patients in the trial developed a condition termed 'cytokine storm', where the massive overproduction of cytokines (a group of chemicals cells use to communicate) by the genetically-invigorated T cells led to their blood pressure plummeting and fevers spiking. Additionally, as the target-molecule CD19 is expressed by both cancerous and healthy white blood cells, T cells are unable to discriminate between the two, leading to all of the body's B cells being destroyed. Patients without B cells are more susceptible to infection.

Typically, pharmaceutical companies have been wary of such therapies, not least due to the difficulties in obtaining regulatory approval. Meanwhile, the research team is currently pursuing a larger trial of over 50 participants to further study the effects of this experimental treatment.

http://www.bionews.org.uk/page_271062.asp

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