Anti-CD3 x EGFR bispecific antibody redirects cytokine-induced killer cells to glioblastoma in vitro and in vivo. 2015

Pan Ma, and Qiang He, and Wei Li, and Xianliang Li, and Huamin Han, and Mengmeng Jin, and Changzhen Liu, and Hua Tao, and Juan Ma, and Bin Gao
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, P.R. China.

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.

UI MeSH Term Description Entries
D007167 Immunotherapy Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. Immunotherapies
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D005909 Glioblastoma A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. Astrocytoma, Grade IV,Giant Cell Glioblastoma,Glioblastoma Multiforme,Astrocytomas, Grade IV,Giant Cell Glioblastomas,Glioblastoma, Giant Cell,Glioblastomas,Glioblastomas, Giant Cell,Grade IV Astrocytoma,Grade IV Astrocytomas
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017252 CD3 Complex Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA). Antigens, CD3,CD3 Antigens,T3 Antigens,CD3 Antigen,T3 Antigen,T3 Complex,Antigen, CD3,Antigen, T3,Antigens, T3
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D055612 Cytokine-Induced Killer Cells Mononuclear leukocytes that have been expanded in CELL CULTURE and activated with CYTOKINES such as INTERLEUKIN-2 to produce large numbers of highly cytotoxic cells. CIK Cells,Lymphocyte-Activated Killer Cell,Lymphocyte-Activated Killer Cells,CIK Cell,Cell, Lymphocyte-Activated Killer,Cells, Lymphocyte-Activated Killer,Cytokine Induced Killer Cells,Cytokine-Induced Killer Cell,Killer Cell, Cytokine-Induced,Killer Cell, Lymphocyte-Activated,Killer Cells, Cytokine-Induced,Killer Cells, Lymphocyte-Activated,Lymphocyte Activated Killer Cell,Lymphocyte Activated Killer Cells

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