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.
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.
Guo
Hongxing
H
State Key Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Science, Peking Union Medical College, Tianjin, China.
Jiang
Wenguo
W
Liu
Wenge
W
Gao
Yingdai
Y
Yang
Ming
M
Zhou
Yuan
Y
Wang
Jinhong
J
Qi
Jing
J
Cheng
Xin
X
Zhu
Zhenping
Z
Yang
Chunzheng
C
Xiong
Dongsheng
D
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
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