title: Bispecific anti-CD3 x anti-HER2 antibody mediates T cell cytolytic activity to HER2-positive colorectal cancer in vitro and in vivo.
abstract: Targeting HER2 overexpressed breast cancer cells with anti‑HER2 monoclonal antibodies inhibits tumor growth. Here we investigated whether HER2 can serve as a target for T cell-mediated immunotherapy of human colorectal carcinoma. Specific cytolytic activity of activated T cells (ATCs) armed with anti‑CD3 x anti‑HER2 bispecific antibody (HER2Bi-Ab) against HER2+ tumor cells was evaluated by bioluminescent signal generated by luciferase reporter on tumor cells in vitro and in vivo. In contrast to unarmed ATCs, increased cytotoxic activity of HER2Bi-armed ATCs against HER2+ tumor cells was observed. Moreover, HER2Bi-armed ATCs expressed higher level of activation marker CD69 and secreted significantly higher levels of IFN-γ than the unarmed ATC counterpart. In addition, compared with anti‑HER2 mAb (Herceptin®) or unarmed ATC, HER2Bi-armed ATCs showed significant suppression against colorectal carcinoma cells. In colorectal tumor cell xenograft mice, infusion of HER2Bi-armed ATCs successfully inhibited the growth of Colo205-luc cells. The HER2Bi-armed ATCs with anti-tumor effects may provide a promising immunotherapy for colorectal carcinoma in the future.
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), Centre for Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P.R. China.
authors.forename: Huamin
authors.initials: H
authors.lastname: Han
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), Centre for Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Hepatobiliary Surgery, 302 Military Hospital of China, Beijing, P.R. China.
authors.forename: Keming
authors.initials: K
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), Centre for Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), Centre for Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P.R. China.
authors.forename: Changzhen
authors.initials: C
authors.lastname: Liu
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), Centre for Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Beijing Hospital of Traditional Chinese Medicine affiliated to Capital Medical University, Beijing, P.R. China.
authors.forename: Ganlin
authors.initials: G
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), Centre for Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P.R. China.
authors.forename: Pan
authors.initials: P
authors.lastname: Ma
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), Centre for Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), Centre for Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P.R. China.
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), Centre for Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Tao
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), Centre for Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Gao
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000008:administration & dosage* / Q000276:immunology; D017252:CD3 Complex / Q000187:drug effects / Q000276:immunology; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology
chemical_list: D018033:Antibodies, Bispecific; D017252:CD3 Complex; D018719:Erb-b2 Receptor Tyrosine Kinases