Treatment of acute myeloid leukemia by directly targeting both leukemia stem cells and oncogenic molecule with specific scFv-immunolipoplexes as a deliverer.
Acute myeloid leukemia (AML) is characterized by the accumulation of immature myeloid cells in the bone marrow and the suppression of normal hematopoiesis, chemotherapy is currently the most used method to treat AML. The standard chemotherapy results in a more than 50% complete remission rate in AML patients. However, treatment with drugs such as anthracyclines is associated with severe side effects and a high incidence of relapse, the long-term survival of AML is poor. The success of the treatment of acute promyelocytic leukemia with all trans retinoic acid and chronic myeloid leukemia with imatinib mesylate (Gleevec) has led to increased efforts to look for agents for AML targeted therapy. But, most of presented targeted therapy agents do only direct some oncogenic molecules involved in the leukemogenesis of AML, their anti-leukemic efficacy is unsatisfied. Thus, novel therapeutic approaches are required. In recent years, a leukemia stem cells (LSCs) origin for AML has been demonstrated, and some unique immunophenotype and specific molecular features of LSCs have also been identified. With the technique development of Immunoliposomes (antibody-coupled liposomes) and the recombination of the variable regions of heavy and light chains and their integration into a single polypeptide that offer the possibility of using single-chain antibody variable region fragments (scFv) for targeting purposes, here we put the hypothesis that treatment of AML by targeting both LSCs and oncogenic molecule participated in AML pathogenesis, with LSCs-specific scFv-immunolipoplexes as a deliverer, might be possible. If successfully using this approach in practice, LSCs might be selectively eradicated and AML might be cured.
Wang
Guang Ping
GP
Department of Hematology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China. guangpingw@yahoo.com
Qi
Zhen Hua
ZH
Chen
Fang Ping
FP
D006801:Humans; D007128:Immunoglobulin Fragments / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000276:immunology*; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000628:therapy*; D009363:Neoplasm Proteins / Q000502:physiology*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000473:pathology*
D007128:Immunoglobulin Fragments; D007135:Immunoglobulin Variable Region; D009363:Neoplasm Proteins