title: Extracellular domain of 4-1BBL enhanced the antitumoral efficacy of peripheral blood lymphocytes mediated by anti-CD3 x anti-Pgp bispecific diabody against human multidrug-resistant leukemia.
abstract: Our previous data have shown a significantly higher tumor response to anti-CD3/anti-Pgp bispecific diabody-mediated immunotherapy for P-glycoprotein (Pgp)-overexpressing K562/A02 cells, but a rapid tumor relapse occurred at 1 week after therapy. In an attempt to overcome tumor recurrence, we supplemented the previous therapy with extracellular domain of human 4-1BBL (ex4-1BBL) to regulate the activation of peripheral blood lymphocyte (PBL). As a result, this combination showed enhanced cytotoxicity in vitro and eradicated the multidrug-resistant xenografts of K562/A02 in nude mice. Furthermore, no tumor recurrence was observed within 100 days after the first treatment. Therefore, when used as an adjuvant, ex4-1BBL may improve the outcome of PBL-based immunotherapy.
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Science, Peking Union Medical College, Tianjin, China.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Guo
authors.forename: Wenguo
authors.initials: W
authors.lastname: Jiang
authors.forename: Wenge
authors.initials: W
authors.lastname: Liu
authors.forename: Yingdai
authors.initials: Y
authors.lastname: Gao
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jinhong
authors.initials: J
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Qi
authors.forename: Xin
authors.initials: X
authors.lastname: Cheng
authors.forename: Zhenping
authors.initials: Z
authors.lastname: Zhu
authors.forename: Chunzheng
authors.initials: C
authors.lastname: Yang
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Xiong
mesh_terms: D053330:4-1BB Ligand / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000276:immunology*; D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology / Q000627:therapeutic use*; D017252:CD3 Complex / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000276:immunology; D019169:Jurkat Cells; D020014:K562 Cells; D007938:Leukemia / Q000276:immunology / Q000628:therapy*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017434:Protein Structure, Tertiary; D011897:Random Allocation; D013047:Specific Pathogen-Free Organisms; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
chemical_list: D053330:4-1BB Ligand; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018033:Antibodies, Bispecific; D017252:CD3 Complex; D007376:Interleukin-2; C505714:TNFRSF9 protein, human; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9