Publication Date:
2016-12-02
Description:
Acute myeloid leukemia (AML) is a heterogeneous myeloid neoplasm with complex pathophysiology. The diversities of karyotype, genetic mutations and epigenetic aberrations in AML result in difficult risk stratification and treatment selection. Despite the application of standard chemotherapies and immunotherapies, many AML patients relapse at least in part due to the failure to eradicate AML leukemic stem cells (LSC). New therapies to target these cells would be immensely valuable. CD33 is a widely expressed myeloid marker present on the majority of AML cells, and CD33-targeted immunotherapies have shown promising results. However, the majority of LSC lack CD33 expression and are not eliminated with such agents. CD123, the alpha chain of the interleukin-3 receptor (IL-3R) heterodimer, is expressed on the majority of LSC and in many AML tumor cells. Several efforts to target CD123 to eradicate LSC have emerged. To date, however, each of these agents exhibited shortcomings that limited their development. SL-401 (from Stemline Therapeutics, NY) is a recombinant fusion protein consisting of human IL-3 and truncated diphtheria toxin. IL-3 dictates the specificity for CD123expressing cells, and the catalytic unit of diphtheria toxin upon internalization inhibits the translational machinery to initiate cell death. SL-401 induced potent, dose-dependent (10, 100, 1000 ng/ml) cytotoxicity in AML patient cells ex vivo, as observed by annexin V/propidium iodide staining. (N=16, 48hr trend p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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