title: Anti-tumor effects of anti-T-cell globulin.
abstract: In vivo T-cell depletion using anti-T-cell antibodies is a standard procedure during allogeneic hematopoietic stem cell transplantation (allo-HSCT). Clinical data demonstrate that in vivo T-cell depletion with the anti-CD52 monoclonal antibody Alemtuzumab is associated with increased relapse rates of hematologic malignancies after allo-HSCT, underlining the importance of donor T cells for graft versus tumor activity. In contrast, recent results suggest that in vivo T-cell depletion with rabbit anti-T-cell globulin (ATG) Fresenius is not associated with tumor relapse after allo-HSCT, raising the possibility that ATG mediates antitumor effects. However, data on ATG's ability to bind to tumor cells and on its effect on the induction of antibody-dependent cellular cytotoxicity (ADCC) are lacking. We used ATG Fresenius, which contains polyclonal rabbit IgG directed against the human T-lymphoma cell line Jurkat, to study relevant mechanisms of ATG-mediated antitumor effects, including ADCC, complement-dependent cytotoxicity, and induction of apoptosis. Based on the knowledge that Jurkat cells aberrantly express myeloid markers and B-cell markers, we hypothesized that rabbit ATG Fresenius binds to a variety of hematologic malignancies. We found that ATG specifically binds to a variety of hematologic malignancies including acute myeloid leukemia and B-cell lymphoma in a concentration-dependent manner. We demonstrate that ATG mediates antitumor activity, including induction of ADCC, complement-dependent cytotoxicity, and apoptosis, toward different hematologic malignancies. Our results contribute to a better understanding of the effects of ATG on posttransplant immunology in patients undergoing allo-HSCT.
authors.affiliation: Department of Hematology, Oncology and Tumorimmunology, Charité Campus Virchow, Klinikum, Berlin, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Westphal
authors.affiliation: Department of Hematology, Oncology and Tumorimmunology, Charité Campus Virchow, Klinikum, Berlin, Germany.
authors.forename: Hanna
authors.initials: H
authors.lastname: Brinkmann
authors.affiliation: Department of Hematology, Oncology and Tumorimmunology, Charité Campus Virchow, Klinikum, Berlin, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Kalupa
authors.affiliation: Department of Hematology, Oncology and Tumorimmunology, Charité Campus Virchow, Klinikum, Berlin, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Wilke
authors.affiliation: Neovii Biotech, Gräfelfing, Germany.
authors.forename: Isabell
authors.initials: I
authors.lastname: Seitz-Merwald
authors.affiliation: Department of Hematology, Oncology and Tumorimmunology, Charité Campus Virchow, Klinikum, Berlin, Germany. Electronic address: olaf.penack@charite.de.
authors.forename: Olaf
authors.initials: O
authors.lastname: Penack
mesh_terms: D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D000937:Antigen-Antibody Reactions; D000961:Antilymphocyte Serum / Q000276:immunology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D018958:CD55 Antigens / Q000276:immunology; D018957:CD59 Antigens / Q000276:immunology; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D004354:Drug Screening Assays, Antitumor; D019337:Hematologic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000627:therapeutic use; D019169:Jurkat Cells / Q000276:immunology; D008212:Lymphocyte Depletion; D010954:Plasmacytoma / Q000473:pathology; D011485:Protein Binding; D011817:Rabbits; D044967:Serum; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000961:Antilymphocyte Serum; D018958:CD55 Antigens; D018957:CD59 Antigens; D007074:Immunoglobulin G; C051590:CD59 protein, human