Stem cell step forward in cancer treatment

Cancer Research UK scientists have developed a new technique for transplanting stem cells into patients which could improve treatments for advanced leukaemia and lymphoma.

The system – in which donor stem cells are genetically engineered to make them resistant to chemotherapy – has the potential to make transplants safer and more effective, lead researcher Dr Raj Chopra will reveal¹.

Stem cell transplantation is one example of how stem cell research has already benefited cancer patients. Dr Chopra – working at the Paterson Institute in collaboration with Dr Lez Fairbarn – has developed the new technique after isolating stem cells from donated bone marrow.

Stem cell transplants may be used to treat leukaemias and lymphomas that have not responded to normal therapies. While a patient’s own immune system is often powerless to stop cancer’s progression, transplants can produce an anti-cancer immune response. Stem cells have the potential to generate many types of adult cell – including cells of the immune system, which recognise and kill cancer cells.

But transplantation is often followed by high-dose chemotherapy, which may cause side effects and can kill the donor cells. Dr Chopra’s team recently carried out a clinical trial with lower doses of chemotherapy and found patients did generate an anti-cancer immune response, but often later suffered from recurrence of their disease.

To counter this problem, the Paterson teams grew stem cells in the laboratory and used a virus to genetically engineer them with a specially selected gene. The gene – called Atase – confers resistance to the toxic effects of chemotherapy and enhances the survival of donor stem cells in patients receiving chemotherapy. This should now enable high-dose chemotherapy to be given if leukaemia or lymphoma recurs after a transplant.

Dr Raj comments: “Our new system, which we call genetic chemoprotection, prevents donor stem cells from being harmed by chemotherapy and so should allow us to use much higher doses than would otherwise be possible.”

Treating patients with high doses of chemotherapy following their transplant seems to have a double action against cancer.

As well as attacking cancer cells, chemotherapy also kills off the patient’s own stem cells, leaving only the transplanted stem cells alive. These then multiply to fill the gaps, strengthening the anti-cancer immune response and increasing the effectiveness of the transplant.

Dr Chopra explains: “The immune response is entirely generated by the cells we’ve transplanted. The higher the proportion of donated stem cells, the stronger will be the immune system’s anti-cancer effect. The end-point is a treatment with the potential to be doubly effective.”

As well as focusing on developing the new technique in patients, Dr Chopra is also planning to study human embryonic stem cells. These may have the ability to generate a wider variety of adult cells than cells taken from bone marrow and so could have the potential to provide more potent treatments.

Dr John Toy, Medical Director of Cancer Research UK, says: “There’s a real need to develop innovative new treatments for those patients whose cancers are resistant to conventional therapies.

“Dr Chopra’s research combines two of the most exciting areas of medical science – stem cell research and gene therapy – to create a really clever potential treatment which may end up saving lives.”

ENDS

1. Speaking at the charity’s first annual conference in Kenilworth, Warwickshire

Note to Editors:

In the trial of non-engineered stem cells, researchers treated 38 patients with advanced Hodgkin’s Disease and Non Hodgkin’s Lymphoma and found that 53 per cent survived 14 months after treatment. Without receiving transplants, the patients would have been expected to survive 10.5 months in the case of advanced Hodgkin’s Disease and three months with advanced Non Hodgkin’s Lymphoma. Scientists hope that the use of genetically engineered donor cells could further improve transplants.