Anti-CD3 x EGFR bispecific antibody redirects cytokine-induced killer cells to glioblastoma in vitro and in vivo

• DOI: 10.3892/or.2015.4233
• Publication Date: 2015-08-28T07:20:26Z
• Authors: PAN MA; QIANG HE; WEI LI; XIANLIANG LI; HUAMIN HAN; MENGMENG JIN; CHANGZHEN LIU; HUA TAO; JUAN MA; BIN GAO
• Keywords: CD3 Complex; Cell Survival; In Vitro Techniques; Xenograft Model Antitumor Assays; 3. Good health; ErbB Receptors; Mice; 03 medical and health sciences; Cytokine-Induced Killer Cells; 0302 clinical medicine; Cell Line, Tumor; Antibodies, Bispecific; Animals; Humans; Immunotherapy; Glioblastoma; Cell Proliferation

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.