Scientists have announced a breakthrough discovery in understanding how the body fights leukemia.
They have identified a protein called CD19-ligand (CD19-L) located on the surface of certain white blood cells that facilitates the recognition and destruction of leukemia cells by the immune system.
This work represents the first report of a bioengineered version of CD19-L, a recombinant human biotherapeutic agent, targeting CD19-positive leukemic stem cells.
The study was conducted by researchers at the Children's Center for Cancer and Blood Diseases and The Saban Research Institute of Children's Hospital Los Angeles.
B-lineage acute lymphoblastic leukemia (ALL) is the most common cancer occurring in children and adolescents. Despite having received intensive chemotherapy, some patients have recurring disease. For these individuals, the prospect of long-term survival is poor.
Lymphocytes are a type of white blood cell involved in immune function and are categorized 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 the CD19 receptor on the surface of B-lineage leukemia cells, and most importantly on leukemic stem cells responsible for the survival and expansion of the leukemia cell population.
Once the CD19-L binds to leukemia cells, cell death occurs. Although CD19 is abundantly expressed on leukemia 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.
Lead author Fatih Uckun and colleagues have bioengineered and prepared a highly purified liquid formulation of the human CD19-L protein.
This recombinant protein not only shows selective binding to leukemia cells but also causes their rapid destruction within 24 hours. Perhaps most importantly, CD19-L killed even those leukemia 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 leukemia by allowing a selective destruction of leukemic stem cells.