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

Rajeswaran Mani; Chi Ling Chiang; Frank W. Frissora; Ribai Yan; Xiaokui Mo; Sivasubramanian Baskar; Christoph Rader; Rebecca Klisovic; Mitch A. Phelps; Ching Shih Chen; Robert J. Lee; John C. Byrd; Robert Baiocchi; L. James Lee; Natarajan Muthusamy

doi:10.1016/j.exphem.2015.04.008

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

Rajeswaran Mani, Chi Ling Chiang, Frank W. Frissora, Ribai Yan, Xiaokui Mo, Sivasubramanian Baskar, Christoph Rader, Rebecca Klisovic, Mitch A. Phelps, Ching Shih Chen, Robert J. Lee, John C. Byrd, Robert Baiocchi, L. James Lee, Natarajan Muthusamy^*

^*Corresponding author for this work

Institute of Biopharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	770-774.e2
Journal	Experimental Hematology
Volume	43
Issue number	9
DOIs	https://doi.org/10.1016/j.exphem.2015.04.008
State	Published - 1 Sep 2015

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Mani, R., Chiang, C. L., Frissora, F. W., Yan, R., Mo, X., Baskar, S., Rader, C., Klisovic, R., Phelps, M. A., Chen, C. S., Lee, R. J., Byrd, J. C., Baiocchi, R., Lee, L. J., & Muthusamy, N. (2015). ROR1-targeted delivery of OSU-2S, a nonimmunosuppressive FTY720 derivative, exerts potent cytotoxicity in mantle-cell lymphoma in vitro and in vivo. Experimental Hematology, 43(9), 770-774.e2. https://doi.org/10.1016/j.exphem.2015.04.008

@article{6344a5d3497f46dba8167778c4e6f348,

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

abstract = "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.",

author = "Rajeswaran Mani and Chiang, {Chi Ling} and Frissora, {Frank W.} and Ribai Yan and Xiaokui Mo and Sivasubramanian Baskar and Christoph Rader and Rebecca Klisovic and Phelps, {Mitch A.} and Chen, {Ching Shih} and Lee, {Robert J.} and Byrd, {John C.} and Robert Baiocchi and Lee, {L. James} and Natarajan Muthusamy",

note = "Publisher Copyright: {\textcopyright} 2015.",

year = "2015",

month = sep,

day = "1",

doi = "10.1016/j.exphem.2015.04.008",

language = "English",

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pages = "770--774.e2",

journal = "Experimental Hematology",

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Mani, R, Chiang, CL, Frissora, FW, Yan, R, Mo, X, Baskar, S, Rader, C, Klisovic, R, Phelps, MA, Chen, CS, Lee, RJ, Byrd, JC, Baiocchi, R, Lee, LJ & Muthusamy, N 2015, 'ROR1-targeted delivery of OSU-2S, a nonimmunosuppressive FTY720 derivative, exerts potent cytotoxicity in mantle-cell lymphoma in vitro and in vivo', Experimental Hematology, vol. 43, no. 9, pp. 770-774.e2. https://doi.org/10.1016/j.exphem.2015.04.008

TY - JOUR

T1 - ROR1-targeted delivery of OSU-2S, a nonimmunosuppressive FTY720 derivative, exerts potent cytotoxicity in mantle-cell lymphoma in vitro and in vivo

AU - Mani, Rajeswaran

AU - Chiang, Chi Ling

AU - Frissora, Frank W.

AU - Yan, Ribai

AU - Mo, Xiaokui

AU - Baskar, Sivasubramanian

AU - Rader, Christoph

AU - Klisovic, Rebecca

AU - Phelps, Mitch A.

AU - Chen, Ching Shih

AU - Lee, Robert J.

AU - Byrd, John C.

AU - Baiocchi, Robert

AU - Lee, L. James

AU - Muthusamy, Natarajan

PY - 2015/9/1

Y1 - 2015/9/1

N2 - 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.

AB - 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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SN - 0301-472X

VL - 43

SP - 770-774.e2

JO - Experimental Hematology

JF - Experimental Hematology

IS - 9

ER -

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

Abstract

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