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publicado em 24/02/2011 às 14h09:00
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Identified protein that facilitates the destruction of leukemic cells

CD19-L is expressed on the surface of T cells and allows them to selectively bind to the receptor

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Scientists at Children's Center for Cancer and Blood Diseases and the Saban Research Institute at Children's Hospital Los Angeles, United States, announced

breakthrough in understanding how the body fights against leukemia.

Scientists have identified a protein called CD19 ligand (CD19-L), located on the surface of certain white blood cells that facilitates recognition and destruction of leukemia cells by the immune system. This work represents the first report of a bioengineered version of L-CD19, a human recombinant biotherapeutic agents targeting the leukemic stem cell CD19-positive.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children and adolescents. Despite receiving intensive chemotherapy, some patients have disease recurrence. For these individuals, the prospect of long-term survival is poor.

"We need new anti-leukemia therapies capable of killing leukemia cells resistant to chemotherapy in patients with ALL," said Fatih Uckun, first author on the paper which was published in the British Journal of Haematology. "These cells are the most difficult to treat. The challenge is to kill those cells, leaving healthy cells intact."

Lymphocytes, a type of white blood cell involved in immune function, are categorized as B cells or T cells The CD19-L, the newly discovered element, is expressed on the surface of T cells and allows them to bind selectively to the CD19 receptor on the surface of leukemia cells of B lineage, leukaemic stem cells responsible for the survival and expansion of cell population leukemia.

Since the CD19-L binds to leukemia cells, cell death occurs. Although the element is abundantly expressed in cells of leukemia patients with B-lineage ALL, is absent in red cells, T cells and normal bone marrow, making it specific and therefore a good therapeutic target.

Uckun and colleagues bioengineering prepared a liquid formulation of highly purified human protein CD19-L. This recombinant protein not only shows selective binding to leukemia cells, but also causes its rapid destruction in 24 hours. The CD19-L even those killed leukemia cells that were highly resistant to both drugs to standard chemotherapy and radiation.

The identification of CD19-L can lead to innovative therapy for childhood leukemia, allowing selective destruction of leukemic stem cells.

According Uckun, the next step is to carefully evaluate this new agent for clinical potential against leukemia and confirmed in preclinical studies is the destruction of leukemic cells can be achieved with non-toxic doses.

"The CD19 ligand, provides a defense system against previously unrecognized leukemia and opens a new range of therapeutic possibilities for treatment of leukemia," said Stuart Siegel, director of the Center for Cancer and Blood Diseases at Children's Hospital Los Angeles .

   Palavras-chave:   Protein    CD19    Leukemia    ALL    Relapse    Therapeutic target   
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