title: Simultaneous targeting of IL2 and IL12 to Hodgkin's lymphoma cells enhances activation of resting NK cells and tumor cell lysis.
abstract: Hodgkin's disease (HD) is characterized by the accumulation of functionally anergic T cells in the vicinity of the malignant Hodgkin/Reed-Sternberg (H/RS) cells. To revert cellular anergy against H/RS cells, we generated an anti-CD30-antibody-interleukin-(IL)-2 and an anti-CD30-antibody-IL12 fusion protein that target IL2 and IL12, respectively, specifically to CD30+ H/RS cells. Both antibody-cytokine fusion proteins act cooperatively in the activation of resting NK cells, the induction of IFN-g gamma secretion and enhanced target cell lysis. The cooperative activity of the targeted cytokines suggests that the application of both antibody-cytokine fusion proteins may be particularly suitable for the specific immunotherapy of Hodgkin's lymphoma.
authors.affiliation: Department I of Internal Medicine, Tumor Genetics, and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Köln, Germany. andreas.hombach@medizin.uni-koeln.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Hombach
authors.forename: Claudia
authors.initials: C
authors.lastname: Heuser
authors.forename: Hinrich
authors.initials: H
authors.lastname: Abken
mesh_terms: D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy; D003602:Cytotoxicity, Immunologic; D006689:Hodgkin Disease / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007128:Immunoglobulin Fragments / Q000235:genetics*; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics*; D007376:Interleukin-2 / Q000235:genetics*; D017730:Ki-1 Antigen / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D007128:Immunoglobulin Fragments; D007376:Interleukin-2; D017730:Ki-1 Antigen; D011993:Recombinant Fusion Proteins; D018664:Interleukin-12; D007371:Interferon-gamma