Killer T cell treatment shows promise against cancers in transplant patients

Cancer Research UK

 

Blood cell donations could be used to treat transplant patients with a particular form of cancer, according to a Cancer Research UK study reported in the journal Blood1 today (Wednesday).

A team of researchers at the University of Edinburgh generated killer T cells from healthy Scottish blood donors and injected them into patients with a type of blood cell cancer called PTLD2. This form of cancer is caused by a virus in transplant patients whose immune systems have been suppressed to stop their new organ from being rejected and affects up to around 10 per cent of transplant patients.

Around two thirds of patients responded to the treatment. If further trials are successful, a single bank of T cells could potentially serve as a global source of immune cells to treat the condition.

PTLD is caused by the Epstein-Barr virus, a viral infection that over 90 per cent of adults carry. Normally the virus causes no ill effects but it can reactivate in transplant patients and cause PTLD.

Because children are less likely to have been previously exposed to the virus, they are more prone to develop PTLD when they meet the virus for the first time after transplant.

Lead researcher Dr Tanzina Haque, now at the Royal Free and University College Medical School, London, said: "EBV infection after transplantation carries a high risk of PTLD. Our results are encouraging and show that T cell therapy could present a safe alternative treatment for the disease."

The findings of a smaller study using the same technique involving four children and four adults were published in the Lancet3 in 2002 and the treatment's first success was for an eighteen month-old boy from West Yorkshire who developed the disease following a liver and bowel transplant.

In this study - the first phase II clinical trial4 of this approach to the treatment - researchers treated 33 people, ten of whom were children. They used killer T cells taken from healthy blood donors who had already been exposed to EBV. These cells naturally recognise proteins belonging to EBV and kill virus-infected PTLD cells.

After six months, 26 patients were still alive. Of these, 14 patients' tumours had been completely destroyed. In 3 other patients, the tumours shrank to at least half their original size. Thirteen patients with initial complete response remained free of PTLD for up to 7.5 years.

Study director and team leader Professor Dorothy Crawford from University of Edinburgh said: "Current treatments for PTLD include reducing immunosuppression along with chemotherapy, radiotherapy and the drug rituximab. These are all associated with side-effects and do not always successfully treat the condition. This new treatment is proving to be effective and has no toxic effects."

Prof Crawford added that the researchers are now planning to create a new blood bank to enable a larger scale study.

Kate Law, director of clinical trials at Cancer Research UK, said: "The results of this study are exciting for transplant patients at risk of PTLD, particularly young children who are more prone to the condition. We hope further trials using this treatment will confirm its power to help people with this type of cancer."

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Notes to Editor

  1. "Allogeneic cytotoxic T-cell therapy for EBV-positive posttransplantation lymphoproliferative disease: results of a phase 2 multicenter clinical trial" Haque, T. et al. (2007) Blood. doi: 10.1182/blood-2006-12-063008.
  2. Post-Transplant Lymphoproliferative Disease.
  3. "Treatment of Epstein-Barr-virus-positive post-transplantation lymphoproliferative disease with partly HLA-matched allogeneic cytotoxic T cells" Haque, T. et al. (2002) The Lancet.
  4. Phase II clinical trials test treatments on a group of people following a Phase I trial on a smaller group that showed promising results.

Visit CancerHelp UK for more information on EBV as a cause of cancer.

This treatment was developed in the US to treat bone marrow recipients. Scientists used cells taken from the bone marrow donor. As donations of solid organs usually come from people who have died and cannot provide blood donations, the treatment has in the past been modified to use the PTLD patient's own T cells that were artificially stimulated to recognise EBV - a time consuming process. Researchers in this study have used a different approach and taken cells from blood donors who had previously been exposed to EBV and established a T cell bank thus enabling the treatment to be offered more rapidly.

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