Anti-CD3 x EGFR bispecific antibody redirects cytokine-induced killer cells to glioblastoma in vitro and in vivo.
The epidermal growth factor receptor (EGFR) is an attractive target for the immunotherapy of EGFR+ tumors. Adjuvant immunotherapy with cytokine-induced killer (CIK) cells may improve progression-free survival rates in patients suffering from cancer. In the present study, we examined the bispecific antibody anti-CD3 x anti-EGFR (EGFRBi-Ab) for its ability to redirect CIK cells to target EGFR-positive glioblastoma. The specific cytolytic activity of CIK cells armed with EGFRBi-Ab against U87MG-luc cells was evaluated by bioluminescent signal generated using luciferase reporter assay which did not alter the surface molecule expression or proliferation ability of U87MG cells. In contrast to unarmed CIK cells, increased cytotoxic activity of EGFRBi-armed CIK cells against the U87MG-luc target was observed at effector/target (E/T) ratios of 5:1, 10:1, and 20:1. Moreover, EGFRBi-armed CIK cells secreted significantly higher levels of IFN-γ, TNF-α, and IL-2 than their unarmed CIK counterpart cells. Furthermore, in glioblastoma xenograft mice, infusion of the EGFRBi-armed CIK cells successfully inhibited the growth of glioblastoma tumors. The in vitro and in vivo antitumor effects of EGFRBi-armed CIK cells support their clinical use for treatment of glioblastoma in the future.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
Pan
P
Ma
The Beijing Chao-Yang Hospital Capital Medical University, Beijing 100020, P.R. China.
Qiang
Q
He
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
Wei
W
Li
The Beijing Chao-Yang Hospital Capital Medical University, Beijing 100020, P.R. China.
Xianliang
X
Li
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
Huamin
H
Han
The General Hospital of Chinese People's Liberation Army, Beijing 100853, P.R. China.
Mengmeng
M
Jin
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
Changzhen
C
Liu
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
Hua
H
Tao
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
Juan
J
Ma
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
Bin
B
Gao
D000818:Animals; D018033:Antibodies, Bispecific / Q000008:administration & dosage* / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D055612:Cytokine-Induced Killer Cells / Q000276:immunology* / Q000637:transplantation*; D066246:ErbB Receptors / Q000276:immunology*; D005909:Glioblastoma / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D066298:In Vitro Techniques; D051379:Mice; D023041:Xenograft Model Antitumor Assays
D018033:Antibodies, Bispecific; D017252:CD3 Complex; C512478:EGFR protein, human; D066246:ErbB Receptors