![Sample our Bioscience journals, sign in here to start your access, Latest two full volumes FREE to you for 14 days]({"type":"image" , "src" : "/sda/5925/TOC-Subject-Sample-2021-Bioscience.jpg"})
Abstract
Inhibition of the autophagic pathway has recently revealed promising results in increasing pro-death activity of multiple cancer therapeutics. Here, we discuss our findings regarding the autophagy-blocking and anti-neoplastic effects of a synthetic sphingosine analog, FTY720, in mantle cell lymphoma (MCL). We also emphasize how FTY720 enhances the pro-death activity of the fully humanized monoclonal antibody milatuzumab by inhibiting the autophagy-lysosome dependent degradation of its therapeutic target, CD74. Our results provide justification for further evaluation of FTY720 and milatuzumab as a combination therapy for this aggressive B-cell malignancy.
Acknowledgments
Milatuzumab was kindly provided by Dr. D. Goldenberg, Garden State Cancer Center, Center for Molecular Medicine and Immunology, Morris Plains, NJ USA. FTY720 was kindly provided by Dr. Natarajan Muthusamy, Division of Hematology, Department of Medicine, College of Medicine, Ohio State University, Columbus, Ohio, USA. OSU-2S, a nonphosphorylatable FTY720 derivative recently developed at Ohio State University was kindly provided by Dr. C.-S. Chen, Division of Medicinal Chemistry, Ohio State University, Columbus, OH USA. This research was supported by grants from the Lymphoma Research Foundation’s Mantle Cell Lymphoma Research Initiative (R.A.B), the American Cancer Society (ODSR 2009-2 and IRG-67-003-47, M.P-I).