Elsevier

Experimental Hematology

Volume 43, Issue 9, September 2015, Pages 770-774.e2
Experimental Hematology

Brief Communication
ROR1-targeted delivery of OSU-2S, a nonimmunosuppressive FTY720 derivative, exerts potent cytotoxicity in mantle-cell lymphoma in vitro and in vivo

https://doi.org/10.1016/j.exphem.2015.04.008Get rights and content
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Highlights

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    OSU-2S exhibits potent cytotoxicity in mantle-cell lymphoma

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    OSU-2S increases the surface expression of CD74 in mantle-cell lymphoma

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    ROR1-targeted OSU-2S immunonanoparticle is active 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.

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