title: Anti-human CD138 monoclonal antibodies and their bispecific formats: generation and characterization.
abstract: Syndecan-1 (CD138), a heparan sulfate proteoglycan, acts as a co-receptor for growth factors and chemokines and is a molecular marker associated with the epithelial-mesenchymal transition during development and carcinogenesis. In this study, we generated two specific mouse anti-human CD138 monoclonal antibodies (mAbs, clone ID: 480CT5.4.3, 587CT7.3.6.5) using hybridoma technology and identified their immunological characteristics. After hybridoma sequencing, the single-chain variable fragments (ScFvs) cloned from two hybridoma cells were combined with anti-CD3 OKT-3 ScFv to generate two recombinant bispecific antibodies (h-STL002, m-STL002) against CD138 and CD3 molecules, respectively. The bispecific antibodies were able to specifically target CD138 + multiple myeloma (MM) cells and CD3 + T cells, and showed the potent cytotoxicity against MM RPMI-8226 cell line through T cell activation. However, these bispecific antibodies without T cells did not cause toxic side effect on MM cells. Overall, the two hybridoma clones and their bispecific formats have great potential to promote diagnosis and immunotherapy of plasma cell malignancy.
authors.affiliation: a The Cyrus Tang Hematology Center , Soochow University , Suzhou , Jiangsu , PR China ;|b Collaborative Innovation Center of Hematology , Soochow University , Suzhou , Jiangsu , PR China ;
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.affiliation: a The Cyrus Tang Hematology Center , Soochow University , Suzhou , Jiangsu , PR China ;|b Collaborative Innovation Center of Hematology , Soochow University , Suzhou , Jiangsu , PR China ;|c Abgent (Suzhou) Biotechnology Co., Ltd. , Suzhou , Jiangsu , PR China ;
authors.forename: Jianxuan
authors.initials: J
authors.lastname: Zou
authors.affiliation: a The Cyrus Tang Hematology Center , Soochow University , Suzhou , Jiangsu , PR China ;|b Collaborative Innovation Center of Hematology , Soochow University , Suzhou , Jiangsu , PR China ;|d Persongen Biomedicine (Suzhou) Co., Ltd. , Suzhou , Jiangsu , PR China ;
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Zong
authors.affiliation: a The Cyrus Tang Hematology Center , Soochow University , Suzhou , Jiangsu , PR China ;|b Collaborative Innovation Center of Hematology , Soochow University , Suzhou , Jiangsu , PR China ;
authors.forename: Huimin
authors.initials: H
authors.lastname: Meng
authors.affiliation: a The Cyrus Tang Hematology Center , Soochow University , Suzhou , Jiangsu , PR China ;|b Collaborative Innovation Center of Hematology , Soochow University , Suzhou , Jiangsu , PR China ;
authors.forename: Gangli
authors.initials: G
authors.lastname: An
authors.affiliation: a The Cyrus Tang Hematology Center , Soochow University , Suzhou , Jiangsu , PR China ;|b Collaborative Innovation Center of Hematology , Soochow University , Suzhou , Jiangsu , PR China ;|e Suzhou Cancer Immunotherapy-Diagnosis and Nanomedicine Engineering Technology Center , Suzhou , Jiangsu , PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D053668:Syndecan-1 / Q000276:immunology*
chemical_list: D018033:Antibodies, Bispecific; D058846:Antibodies, Monoclonal, Murine-Derived; D017252:CD3 Complex; C508241:SDC1 protein, human; D053668:Syndecan-1
keywords: Bispecific antibodies; ScFv; T cells; multiple myeloma; syndecan-1