title: Generation of single-chain bispecific green fluorescent protein fusion antibodies for imaging of antibody-induced T cell synapses.
abstract: There is growing interest in the development of novel single-chain bispecific antibodies for retargeting of immune effector T cells to tumor cells. Until today, functional fusion constructs consisting of a single-chain bispecific antibody and a fluorescent protein were not reported. Such molecules could be useful for an in vivo visualization of this retargeting process. Recently, we established two novel single-chain bispecific antibodies. One is capable of retargeting T cells to CD33, and the other is capable of retargeting T cells to the prostate stem cell antigen (PSCA). CD33 is an attractive immunotarget on the surface of tumor cells from patients with acute myeloid leukemia (AML). The PSCA is a potential target on prostate cancer cells. Flanking the reading frame encoding the green fluorescent protein (GFP) with a recently described novel helical linker element allowed us to establish novel single-chain bispecific fusion antibodies. These fluorescent fusion antibodies were useful to efficiently retarget T cells to the respective tumor cells and visualize the formation of immune synapses between effector and target cells.
authors.affiliation: Institute of Immunology, Medical Faculty Carl Gustav Carus, Technical University Dresden, 01307 Dresden, Germany.
authors.forename: Slava
authors.initials: S
authors.lastname: Stamova
authors.forename: Anja
authors.initials: A
authors.lastname: Feldmann
authors.forename: Marc
authors.initials: M
authors.lastname: Cartellieri
authors.forename: Claudia
authors.initials: C
authors.lastname: Arndt
authors.forename: Stefanie
authors.initials: S
authors.lastname: Koristka
authors.forename: Falko
authors.initials: F
authors.lastname: Apel
authors.forename: Rebekka
authors.initials: R
authors.lastname: Wehner
authors.forename: Marc
authors.initials: M
authors.lastname: Schmitz
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
authors.forename: Malte
authors.initials: M
authors.lastname: von Bonin
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.forename: Holger
authors.initials: H
authors.lastname: Bartsch
authors.forename: Michael
authors.initials: M
authors.lastname: Bachmann
mesh_terms: D018033:Antibodies, Bispecific / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D045744:Cell Line, Tumor; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D054992:Immunological Synapses / Q000378:metabolism / Q000473:pathology*; D018613:Microscopy, Confocal; D017430:Prostate-Specific Antigen / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D063268:Sialic Acid Binding Ig-like Lectin 3; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
chemical_list: D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017252:CD3 Complex; C571163:CD33 protein, human; D011993:Recombinant Fusion Proteins; D063268:Sialic Acid Binding Ig-like Lectin 3; D049452:Green Fluorescent Proteins; D017430:Prostate-Specific Antigen