title: A novel human-derived antibody against NY-ESO-1 improves the efficacy of chemotherapy.
abstract: We investigated whether antibodies against intracellular tumor-associated antigens support tumor-specific immunity when administered together with a treatment that destroys the tumor. We propose that released antigens form immune complexes with the antibodies, which are then efficiently taken up by dendritic cells. We cloned the first human monoclonal antibodies against the Cancer/Testis (CT) antigen, NY-ESO-1. We tested whether the monoclonal anti-NY-ESO-1 antibody (12D7) facilitates cross-presentation of a NY-ESO-1-derived epitope by dendritic cells to human CD8+ T cells, and whether this results in the maturation of dendritic cells in vitro. We investigated the efficacy of 12D7 in combination with chemotherapy using BALB/c mice bearing syngeneic CT26 tumors that express intracellular NY-ESO-1. Human dendritic cells that were incubated with NY-ESO-1:12D7 immune complexes efficiently stimulated NY-ESO-1(157-165)/HLA-A2-specific human CD8+ T cells to produce interferon-γ, whereas NY-ESO-1 alone did not. Furthermore, the incubation of dendritic cells with NY-ESO-1:12D7 immune complexes resulted in the maturation of dendritic cells. Treatment of BALB/c mice that bear CT26/NY-ESO-1 tumors with 5-fluorouracil (5-FU) plus 12D7 was significantly more effective than chemotherapy alone. We propose systemic injection of monoclonal antibodies (mAbs) against tumor-associated antigens plus a treatment that promotes the local release of those antigens resulting in immune complex formation as a novel therapeutic modality for cancer.
authors: Department of Oncology, University Hospital Zürich, Zürich, Switzerland.
authors: Anurag
authors: A
authors: Gupta
authors: Natko
authors: N
authors: Nuber
authors: Christoph
authors: C
authors: Esslinger
authors: Mareike
authors: M
authors: Wittenbrink
authors: Martin
authors: M
authors: Treder
authors: Alexandro
authors: A
authors: Landshammer
authors: Takuro
authors: T
authors: Noguchi
authors: Marcus
authors: M
authors: Kelly
authors: Sacha
authors: S
authors: Gnjatic
authors: Erika
authors: E
authors: Ritter
authors: Lotta
authors: L
authors: von Boehmer
authors: Hiroyoshi
authors: H
authors: Nishikawa
authors: Hiroshi
authors: H
authors: Shiku
authors: Lloyd
authors: L
authors: Old
authors: Gerd
authors: G
authors: Ritter
authors: Alexander
authors: A
authors: Knuth
authors: Maries
authors: M
authors: van den Broek
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology*; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects; D003001:Cloning, Molecular; D045142:Cross-Priming / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D018604:Epitope Mapping; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; C104948:CTAG1B protein, human; D008565:Membrane Proteins; D005472:Fluorouracil
keywords: NY-ESO-1; antibody; chemotherapy
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