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
N1 - Publisher Copyright:
© 2015.
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.
UR - https://www.scopus.com/pages/publications/84940453671
UR - https://www.scopus.com/pages/publications/84940453671#tab=citedBy
U2 - 10.1016/j.exphem.2015.04.008
DO - 10.1016/j.exphem.2015.04.008
M3 - Article
C2 - 25937048
AN - SCOPUS:84940453671
SN - 0301-472X
VL - 43
SP - 770-774.e2
JO - Experimental Hematology
JF - Experimental Hematology
IS - 9
ER -
