Scientists `bioengineer` protein to fight leukaemia

Washington: Scientists claim to have made a major advancement in understanding how the human body fights leukaemia, a finding which may pave the way for better and effective treatment for the disease.

A team in the US has actually identified a protein, CD19-ligand (CD19-L) located on the surface of certain white blood cells that facilitates the recognition and destruction of leukaemia cells by the immune system, `British Journal of Haematology` reported.

The work by the scientists from the Children`s Center for Cancer and Blood Diseases and Saban Research Institute of Children`s Hospital, Los Angeles, represents the first report
of a bioengineered version of CD19-L, a recombinant human bio- therapeutic agent targeting CD19-positive leukemic stem cells.

B-lineage acute lymphoblastic leukaemia (ALL) is the most common cancer occurring in children and adolescents. But, despite having received intensive chemotherapy, some patients have recurring disease. For these individuals, the prospect of long-term survival is poor.

"We need new anti-leukaemia therapies capable of killing chemotherapy-resistant leukaemia cells in patients with relapsed ALL. These are the cells that are the most
difficult to treat. The challenge is to kill these cells while leaving healthy cells intact," said team leader Fatih Uckun.

Lymphocytes are a type of white blood cell involved in immune function and are categorised as either B-cells or T-cells. This newly discovered element, CD19-L, is expressed on the surface of T-lymphocytes and allows them to selectively bind to CD19 receptor on the surface of B-lineage leukaemia cells, and most importantly on leukemic stem cells responsible for survival and expansion of the leukaemia cell population.

Once the CD19-L binds to leukaemia cells, cell death occurs. Although CD19 is abundantly expressed on leukaemia cells from B-lineage ALL patients, it is absent on red cells, T-cells, and normal bone marrow stem cells, making it specific, and therefore, a good therapeutic target.

The scientists have bioengineered and prepared a highly purified liquid formulation of human CD19-L protein. This recombinant protein not only shows selective binding to
leukaemia cells but causes their rapid destruction within 24 hours. Perhaps most importantly, CD19-L killed even those leukaemia cells that were highly resistant to both standard chemotherapy drugs as well as radiation.

The identification of CD19-L may lead to therapeutic innovation for childhood leukaemia by allowing a selective destruction of leukemic stem cells.

"The CD19-ligand offers a previously unrecognized defense system against leukaemia and opens a new range of therapeutic opportunities for the treatment of leukaemia,"
said co-scientist Stuart Siegel.