ROR1-targeted delivery of OSU-2S, a nonimmunosuppressive FTY720 derivative, exerts potent cytotoxicity in mantle-cell lymphoma in vitro and in vivo.
Mantle-cell lymphoma (MCL) remains incurable despite numerous therapeutic advances. OSU-2S, a novel nonimmunosuppressive FTY720 (Fingolimod) derivative, exhibits potent cytotoxicity in MCL cell lines and primary cells. OSU-2S increased the surface expression of CD74, a therapeutic antibody target in MCL cells. OSU-2S, in combination with anti-CD74 antibody milatuzumab, enhanced cytotoxicity in MCL. Moreover, MCL tumor antigen receptor tyrosine kinase-like orphan receptor 1 (ROR1) targeted immunonanoparticle-carrying OSU-2S (2A2-OSU-2S-ILP)-mediated selective cytotoxicity of MCL in vitro, as well as activity in a xenografted mouse model of MCL in vivo. The newly developed OSU-2S delivery using ROR1-directed immunonanoparticles provide selective targeting of OSU-2S to MCL and other ROR1(+) malignancies, sparing normal B cells.
Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA; Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.
Rajeswaran
R
Mani
Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA; Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University, Columbus, OH, USA.
Chi-Ling
CL
Chiang
Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Frank W
FW
Frissora
Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
Ribai
R
Yan
Center for Biostatistics, The Ohio State University, Columbus, OH, USA.
Xiaokui
X
Mo
Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Sivasubramanian
S
Baskar
Department of Cancer Biology and Department of Molecular Therapeutics, The Scripps Research Institute, Scripps Florida, Jupiter, FL, USA.
Christoph
C
Rader
Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA.
Rebecca
R
Klisovic
Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA; Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
Mitch A
MA
Phelps
Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA; Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA; Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
Ching-Shih
CS
Chen
Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA; Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University, Columbus, OH, USA; Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
Robert J
RJ
Lee
Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA; Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA; Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
John C
JC
Byrd
Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA; Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.
Robert
R
Baiocchi
Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University, Columbus, OH, USA; Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, USA.
L James
LJ
Lee
Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA; Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA. Electronic address: raj.muthusamy@osumc.edu.
Natarajan
N
Muthusamy
D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism; D003603:Cytotoxins / Q000494:pharmacology*; D016503:Drug Delivery Systems; D000068876:Fingolimod Hydrochloride; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D011409:Propylene Glycols / Q000494:pharmacology*; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D061067:Antibodies, Monoclonal, Humanized; D000944:Antigens, Differentiation, B-Lymphocyte; D000951:Antigens, Neoplasm; D003603:Cytotoxins; D000949:Histocompatibility Antigens Class II; C560545:OSU-2S; D011409:Propylene Glycols; C045084:invariant chain; C540932:milatuzumab; C078716:ROR1 protein, human; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine