Growth factor toxin fusion proteins for the treatment of leukemia: Preclinical animal studies relevant for human acute myeloid leukemia
In the development of new therapeutic agents to treat malignancies. bacterial and plant toxins are being investigated. Targeting cells with these toxins has been facilitated by chemical conjugation or genetic engineering of the toxin to proteins with cellular binding potential, such as antibodies (immunotoxins.) or growth factors (growth factor toxins or GFtoxins). Chimeric OF-toxins and immullotoxin proteins combine the specificity of the OF or the antibody part to bind to cellular structures with the killing potential of the toxin part. Genetically engineered toxins have been produced from two bacterial toxins: Pseudomonas exotoxin (PE) and Diphtheria toxin (DT). Such PE and DT based fusion proteins have shown potential to treat hemopoietic malignancies. Some degree of clinical benefit has already been reported in phase I and II clinical trials in leukemia and lymphoma. Acute myeloid leukemia (AML) may also benefit from this approach. Myeloid leukemic cells express GF receptors (GFRs) which bind ligands with high affinity followed by rapid internalization of the ligand-receptor complexes. These features provide a rationale for GFtoxin treatment of AML. Because GFRs are also expressed by non-leukemic cells, preclinical animal studies are essential for the evaluation of the potential of these new therapeutic agents to treat leukemia. Animal models will provide insight into the antileukemic effects, and equally relevant, to the most prominent toxic side effects.
|Publisher||Erasmus MC: University Medical Center Rotterdam|
|Promotor||Hagenbeek, A. (Anton)|
|Sponsor||Dutch Cancer Society, Amgen B.V., Novartis, Pharma B.V., Harlan Nederland|
|Keywords||fusion proteins, hematology, leukemia, myeloid leukemia|
Rozemuller, H.. (1997, November 26). Growth factor toxin fusion proteins for the treatment of leukemia: Preclinical animal studies relevant for human acute myeloid leukemia. Erasmus MC: University Medical Center Rotterdam. Retrieved from http://hdl.handle.net/1765/20354