Pre-clinical Specificity and Safety of UC-961, a First-In-Class Monoclonal Antibody Targeting ROR1

被引:93
作者
Choi, Michael Y. [1 ]
Widhof, George F., II [1 ]
Wu, Christina C. N. [1 ]
Cui, Bing [1 ]
Lao, Fitzgerald [1 ]
Sadarangani, Anil [1 ,2 ]
Cavagnaro, Joy [3 ]
Prussak, Charles [1 ]
Carson, Dennis A. [1 ]
Jamieson, Catriona [1 ,2 ]
Kipps, Thomas J. [1 ]
机构
[1] Univ Calif San Diego, Dept Med, Div Hematol Oncol, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Div Regenerat Med, La Jolla, CA 92093 USA
[3] Access Bio, Boyce, VA USA
基金
美国国家卫生研究院;
关键词
AKT; cancer stem cell; Cirmtuzumab; CLL; Wnt receptor; CHRONIC LYMPHOCYTIC-LEUKEMIA; ANTIGEN ROR1; EXPRESSION; RECEPTOR; PSEUDOKINASE; PHENOTYPE; FAMILY; CLL;
D O I
10.1016/j.clml.2015.02.010
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncoembryonic antigen. Because of its expression on the cell surface of leukemia cells from patients with chronic lymphocytic leukemia (CLL), but not on normal B-cells or other postpartum tissues, ROR1 is an attractive candidate for targeted therapies. UC-961 is a first-in-class humanized monoclonal antibody that binds the extracellular domain of ROR1. In this article we outline some of the preclinical studies leading to an investigational new drug designation, enabling clinical studies in patients with CLL. (C) 2015 The Authors. Published by Elsevier Inc.
引用
收藏
页码:S167 / S169
页数:3
相关论文
共 24 条
[1]   Targeting malignant B cells with an immunotoxin against ROR1 [J].
Baskar, Sivasubramanian ;
Wiestner, Adrian ;
Wilson, Wyndham H. ;
Pastan, Ira ;
Rader, Christoph .
MABS, 2012, 4 (03) :349-361
[2]   Safety of Targeting ROR1 in Primates with Chimeric Antigen Receptor-Modified T Cells [J].
Berger, Carolina ;
Sommermeyer, Daniel ;
Hudecek, Michael ;
Berger, Michael ;
Balakrishnan, Ashwini ;
Paszkiewicz, Paulina J. ;
Kosasih, Paula L. ;
Rader, Christoph ;
Riddell, Stanley R. .
CANCER IMMUNOLOGY RESEARCH, 2015, 3 (02) :206-216
[3]   ROR1 is expressed on hematogones (non-neoplastic human B-lymphocyte precursors) and a minority of precursor-B acute lymphoblastic leukemia [J].
Broome, H. Elizabeth ;
Rassenti, Laura Z. ;
Wang, Huan-You ;
Meyer, Lilly M. ;
Kipps, Thomas J. .
LEUKEMIA RESEARCH, 2011, 35 (10) :1390-1394
[4]   Targeting ROR1 Inhibits Epithelial-Mesenchymal Transition and Metastasis [J].
Cui, Bing ;
Zhang, Suping ;
Chen, Liguang ;
Yu, Jianqiang ;
Widhopf, George F., II ;
Fecteau, Jessie-F. ;
Rassenti, Laura Z. ;
Kipps, Thomas J. .
CANCER RESEARCH, 2013, 73 (12) :3649-3660
[5]   Monoclonal antibodies against ROR1 induce apoptosis of chronic lymphocytic leukemia (CLL) cells [J].
Daneshmanesh, A. H. ;
Hojjat-Farsangi, M. ;
Khan, A. S. ;
Jeddi-Tehrani, M. ;
Akhondi, M. M. ;
Bayat, A. A. ;
Ghods, R. ;
Mahmoudi, A-R ;
Hadavi, R. ;
Osterborg, A. ;
Shokri, F. ;
Rabbani, H. ;
Mellstedt, H. .
LEUKEMIA, 2012, 26 (06) :1348-1355
[6]   Antisera induced by infusions of autologous Ad-CD154-leukemia B cells identify ROR1 as an oncofetal,antigen and receptor for Wnt5a [J].
Fukuda, Tetsuya ;
Chen, Liguang ;
Endo, Tomoyuki ;
Tang, Li ;
Lu, Desheng ;
Castro, Jariuario E. ;
Widhopf, George F., II ;
Rassenti, Laura Z. ;
Cantwell, Mark J. ;
Prussak, Charles E. ;
Carson, Dennis A. ;
Kipps, Thomas J. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (08) :3047-3052
[7]   The ROR1 pseudokinase diversifies signaling outputs in MET-addicted cancer cells [J].
Gentile, Alessandra ;
Lazzari, Luca ;
Benvenuti, Silvia ;
Trusolino, Livio ;
Comoglio, Paolo Maria .
INTERNATIONAL JOURNAL OF CANCER, 2014, 135 (10) :2305-2316
[8]   Ror1 Is a Pseudokinase That Is Crucial for Met-Driven Tumorigenesis [J].
Gentile, Alessandra ;
Lazzari, Luca ;
Benvenuti, Silvia ;
Trusolino, Livio ;
Comoglio, Paolo M. .
CANCER RESEARCH, 2011, 71 (08) :3132-3141
[9]   Obinutuzumab plus Chlorambucil in Patients with CLL and Coexisting Conditions [J].
Goede, Valentin ;
Fischer, Kirsten ;
Busch, Raymonde ;
Engelke, Anja ;
Eichhorst, Barbara ;
Wendtner, Clemens M. ;
Chagorova, Tatiana ;
de la Serna, Javier ;
Dilhuydy, Marie-Sarah ;
Illmer, Thomas ;
Opat, Stephen ;
Owen, Carolyn J. ;
Samoylova, Olga ;
Kreuzer, Karl-Anton ;
Stilgenbauer, Stephan ;
Doehner, Hartmut ;
Langerak, Anton W. ;
Ritgen, Matthias ;
Kneba, Michael ;
Asikanius, Elina ;
Humphrey, Kathryn ;
Wenger, Michael ;
Hallek, Michael .
NEW ENGLAND JOURNAL OF MEDICINE, 2014, 370 (12) :1101-1110
[10]  
Green J., 2014, Cold Spring Harb Perspect Biol, V6