title: Eradication of non-Hodgkin lymphoma through the induction of tumor-specific T-cell immunity by CD20-Flex BiFP.
abstract: Although monoclonal antibodies, including CD20 antibody rituximab, are standard therapeutics for several cancers, their efficacy remains variable and often modest. There is an urgent need to enhance the efficacy of the current generation of anticancer antibodies. Flt3 ligand, a soluble protein, has the ability to induce substantial expansion of dendritic cells (DCs). In this study, we constructed a bispecific immunoglobulin G-like bispecific fusion protein (BiFP) targeting both CD20 and Flt3 (CD20-Flex) by using CrossMab technology. We found that the BiFP exhibited stabilities that were comparable with the parental antibody rituximab and were able to bind to both targets with unaltered binding affinity. Notably, our data indicated that CD20-Flex BiFP could not only eliminate lymphoma temporarily but also potentiate tumor-specific T-cell immunity, which affords a long-lasting protection from tumor recurrence. The results showed that the expansion and infiltration of DCs into tumor tissues by CD20-Flex BiFP could be an effective way to generate protective immune responses against cancer, suggesting that the CD20-Flex BiFP could be a promising therapeutic agent against B-cell lymphomas.
authors.affiliation: International Joint Cancer Institute, Second Military Medical University, Shanghai, People's Republic of China;
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Qin
authors.initials: Q
authors.lastname: Tong
authors.forename: Weizhu
authors.initials: W
authors.lastname: Qian
authors.forename: Bohua
authors.initials: B
authors.lastname: Li
authors.forename: Dapeng
authors.initials: D
authors.lastname: Zhang
authors.forename: Tuo
authors.initials: T
authors.lastname: Fu
authors.forename: Shuyan
authors.initials: S
authors.lastname: Duan
authors.forename: Xueguang
authors.initials: X
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.forename: Jianxin
authors.initials: J
authors.lastname: Dai
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Sheng
authors.initials: S
authors.lastname: Hou
authors.forename: Yajun
authors.initials: Y
authors.lastname: Guo
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology / Q000493:pharmacokinetics / Q000494:pharmacology*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology / Q000493:pharmacokinetics / Q000494:pharmacology*; D018951:Antigens, CD20 / Q000276:immunology; D000970:Antineoplastic Agents / Q000276:immunology / Q000493:pharmacokinetics / Q000494:pharmacology; D002478:Cells, Cultured; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D000069283:Rituximab; D013601:T-Lymphocytes / Q000276:immunology*; D051941:fms-Like Tyrosine Kinase 3 / Q000276:immunology
chemical_list: D018033:Antibodies, Bispecific; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D000069283:Rituximab; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3