Antibody development for safer stem cell transplant in acute myeloid leukaemia

26 June 2014

Professor Persis Amrolia, UCL Institute of Child Health

Stem cell transplant is often used to treat patients with acute myeloid leukaemia but the intensive treatment used pre-transplant to destroy the patient’s bone marrow has serious side effects. Professor Amrolia is pioneering a new way of destroying the bone marrow, using specially designed antibodies to create space for the donor stem cells. If successful, this approach should make it possible to carry out transplants in a much safer way.

Amount of grant: £267,162 | Date of award: June 2014


Stem cell transplant (SCT) is an important but high-risk procedure often used in the treatment of children with acute myeloid leukaemia (AML). As part of the preparation for SCT, patients are given intensive chemotherapy and/or radiotherapy to destroy their bone marrow (which contains their blood stem cells, including leukaemic cells) and create space for the new stem cells from the donor.

This intensive ‘conditioning’ treatment has many side-effects. It can damage the lungs, liver and gut and can cause long-term problems with growth, development and fertility. If less intensive treatment is used, however, there is a risk that the leukaemia will return (relapse).

In this project, Professor Amrolia is pioneering a new approach to preparing patients for SCT, avoiding the need for such intensive chemotherapy. He is developing a new immune medicine - an antibody - that targets a protein called c-kit that is expressed on the surface of AML cells and normal stem cells. The antibody will recognise and kill leukaemic cells and bone marrow cells. Importantly, however, it will not target any other cells meaning that it should cause much less toxicity outside the bone marrow.

This team has already made a library of millions of antibody fragments. They have identified a number of fragments that recognise c-kit. The next step is to engineer the fragments into whole antibodies and carry out laboratory tests to see which of these kill normal stem cells and leukaemic cells best.

About the research team

Professor Amrolia is Professor of Transplantation Immunology and UCL Institute of Child Health and Honorary Consultant in Bone Marrow Transplant at Great Ormond Street Hospital (GOSH).

The Bone Marrow Transplant Unit at GOSH has the largest paediatric SCT programme in Europe. Professor Amrolia has been working for 15 years on the development of more gentle methods of transplantation and has an established track record in the translation of basic scientific work into clinical practice for patients undergoing SCT, including a landmark study of antibody-based conditioning in children with genetic diseases.

He is collaborating with Professor Kerry Chester at UCL Cancer Institute, a national expert in the field of antibody engineering, who will provide expertise in the development of the optimal antibody.

Professor Dominique Bonnet at the London Research Institute is a world leader in mouse models of leukaemia and will lead the pre-clinical testing of the antibody.

What difference will this project make?

This project will provide the evidence needed to develop a ‘clinical grade’ anti-c-kit antibody (i.e. one that can be used in patients). This will then enable the first clinical trials to test how safe and effective the combination of this anti-c-kit antibody and gentler chemotherapy conditioning is in patients with AML undergoing SCT.

If successful, this new approach would represent a major breakthrough for both children and adults with AML by preventing leukaemic relapse and reducing the short- and long-term toxicity of chemotherapy, including toxicity to the gut, liver and lungs and infertility.

In addition, the antibodies could be linked to drugs or labeled radioactively, allowing delivery of larger doses directly to the bone marrow in patients at high risk of relapse, so that the chance of the leukaemia coming back can be reduced.

Read more: Acute myeloid leukaemia | Treating childhood cancer


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