Targeting CLL antigens after stem cell transplantation
John Gribben, M.D., DSc.
Barts Cancer Center of Excellence/ The London School of Medicine (UK)
Abstract:
The working hypothesis being examined here is that cancer cells, including CLL cells, express proteins that can be seen as foreign by the immune system. These proteins are the target of donor immune cells following stem cell transplants, an effect known as the "graft versus leukemia" (GVL) effect. Although this effect is well characterized in CLL, it is not known what the target proteins are in CLL cells.
We aim to identify these proteins using molecular techniques and demonstrate that donor immune cells targeting these proteins can be expanded in the test tube and are capable of killing CLL cells. Once we have established this, we shall use the mouse model of CLL to determine if these cells can be given back safely. This will provide the pre-clinical studies that will be required to be able to move on to clinical trials in patients with CLL. In the proposed clinical trial, we would obtain blood samples from matched sibling donors and expand the CLL specific immune cells outside the body that target the proteins identified that are expressed by the CLL cells. These cells would then be infused back to patients with CLL who have undergone stem cell transplants and who still have evidence of disease.
We believe that this approach will increase the cure rate after stem cell transplantation for CLL, as well as decreasing the risk of the procedure. If successful, we would aim also to try to induce immune responses against these proteins using the patients own cells.