Generation and preclinical characterization of an antibody specific for SEMA4D

被引：44

作者：

Fisher, Terrence L. ^{[1
]}

Reilly, Christine A. ^{[1
]}

Winter, Laurie A. ^{[1
]}

Pandina, Tracy ^{[1
]}

Jonason, Alan ^{[1
]}

Scrivens, Maria ^{[1
]}

Balch, Leslie ^{[1
]}

Bussler, Holm ^{[1
]}

Torno, Sebold ^{[1
]}

Seils, Jennifer ^{[1
]}

Mueller, Loretta ^{[1
]}

Huang, He ^{[1
]}

Klimatcheva, Ekaterina ^{[1
]}

Howell, Alan ^{[1
]}

Kirk, Renee ^{[1
]}

Evans, Elizabeth ^{[1
]}

Paris, Mark ^{[1
]}

Leonard, John E. ^{[1
]}

Smith, Ernest S. ^{[1
]}

Zauderer, Maurice ^{[1
]}

机构：

[1] Vaccinex Inc, Rochester, NY 14620 USA

来源：

MABS | 2016年 / 8卷 / 01期

关键词：

arthritis; CD100; humanized monoclonal antibody; Mab; 67-2; Semaphorin; SEMA4D; VX15; 2503; IV SEMAPHORIN CD100; B-CELL; IMMUNE-SYSTEM; LYMPHOCYTE SEMAPHORIN; MONOCLONAL-ANTIBODY; BIOLOGICAL-ACTIVITY; DENDRITIC CELLS; T-LYMPHOCYTES; SOLUBLE CD100; 4D;

D O I：

10.1080/19420862.2015.1102813

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Semaphorin 4D (SEMA4D or CD100) is a member of the semaphorin family of proteins and an important mediator of the movement and differentiation of multiple cell types, including those of the immune, vascular, and nervous systems. Blocking the binding of SEMA4D to its receptors can result in physiologic changes that may have implications in cancer, autoimmune, and neurological disease. To study the effects of blocking SEMA4D, we generated, in SEMA4D-deficient mice, a panel of SEMA4D-specific hybridomas that react with murine, primate, and human SEMA4D. Utilizing the complementarity-determining regions from one of these hybridomas (mAb 67-2), we generated VX15/2503, a humanized IgG4 monoclonal antibody that is currently in clinical development for the potential treatment of various malignancies and neurodegenerative disorders, including multiple sclerosis and Huntington's disease. This work describes the generation and characterization of VX15/2503, including in vitro functional testing, epitope mapping, and an in vivo demonstration of efficacy in an animal model of rheumatoid arthritis.

引用

收藏

页码：150 / 162

页数：13

相关论文

共 47 条

[1] Semaphorin 4D provides a link between axon guidance processes and tumor-induced angiogenesis [J].

Basile, John R. ;

Castilho, Rogerio M. ;

Williams, Vanessa P. ;

Gutkind, J. Silvio .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (24) :9017-9022

[2] Antigenic modulation limits the efficacy of anti-CD20 antibodies: implications for antibody selection [J].

Beers, Stephen A. ;

French, Ruth R. ;

Chan, H. T. Claude ;

Lim, Sean H. ;

Jarrett, Timothy C. ;

Vidal, Regina Mora ;

Wijayaweera, Sahan S. ;

Dixon, Sandra V. ;

Kim, Hyungjin ;

Cox, Kerry L. ;

Kerr, Jonathan P. ;

Johnston, David A. ;

Johnson, Peter W. M. ;

Verbeek, J. Sjef ;

Glennie, Martin J. ;

Cragg, Mark S. .

BLOOD, 2010, 115 (25) :5191-5201

[3] Tumours can act as adjuvants for humoral immunity [J].

Brown, DM ;

Fisher, TL ;

Wei, C ;

Frelinger, JG ;

Lord, EM .

IMMUNOLOGY, 2001, 102 (04) :486-497

[4] Ki-67 and CD100 immunohistochemical expression is associated with local recurrence and poor prognosis in soft tissue sarcomas, respectively [J].

Campos, Marcelo ;

Pegorin De Campos, Silvana Gisele ;

Ribeiro, Guilherme Gomes ;

Eguchi, Flavia Coltri ;

Morini Da Silva, Sandra Regina ;

De Oliveira, Cleyton Zanardo ;

Da Costa, Allini Mafra ;

Curcelli, Emilio Carlos ;

Nunes, Marcos Ceita ;

Penna, Valter ;

Longatto-Filho, Adhemar .

ONCOLOGY LETTERS, 2013, 5 (05) :1527-1535

[5] Roles of Sema4D and Plexin-B1 in tumor progression [J].

Ch'ng, Ewe Seng ;

Kumanogoh, Atsushi .

MOLECULAR CANCER, 2010, 9

[6] Biological activity of soluble CD100.: II.: Soluble CD100, similarly to H-SemaIII, inhibits immune cell migration [J].

Delaire, S ;

Billard, C ;

Tordjman, R ;

Chédotal, A ;

Elhabazi, A ;

Bensussan, A ;

Boumsell, L .

JOURNAL OF IMMUNOLOGY, 2001, 166 (07) :4348-4354

[7] Biological activity of soluble CD100. 1. The extracellular region of CD100 is released from the surface of T lymphocytes by regulated proteolysis [J].

Elhabazi, A ;

Delaire, S ;

Bensussan, A ;

Boumsell, L ;

Bismuth, G .

JOURNAL OF IMMUNOLOGY, 2001, 166 (07) :4341-4347

[8] Antibody Blockade of Semaphorin 4D Promotes Immune Infiltration into Tumor and Enhances Response to Other Immunomodulatory Therapies [J].

Evans, Elizabeth E. ;

Jonason, Alan S., Jr. ;

Bussler, Holm ;

Torno, Sebold ;

Veeraraghavan, Janaki ;

Reilly, Christine ;

Doherty, Michael A. ;

Seils, Jennifer ;

Winter, Laurie A. ;

Mallow, Crystal ;

Kirk, Renee ;

Howell, Alan ;

Giralico, Susan ;

Scrivens, Maria ;

Klimatcheva, Katya ;

Fisher, Terrence L. ;

Bowers, William J. ;

Paris, Mark ;

Smith, Ernest S. ;

Zauderer, Maurice .

CANCER IMMUNOLOGY RESEARCH, 2015, 3 (06) :689-701

[9] Generation of monoclonal antibodies specific for human kallikrein 2 (hK2) using hK2-expressing tumors [J].

Fisher, TL ;

Nocera, M ;

Willis, RA ;

Turner, MJ ;

Alim, CSA ;

Brown, DM ;

Bourne, PA ;

Agnese, PAD ;

Messing, EM ;

Lord, EM ;

Frelinger, JG .

PROSTATE, 2002, 51 (03) :153-165

[10]

Giger RJ, 2010, COLD SPRING HARB PER, V2

← 1 2 3 4 5 →