title: Anti-CD30-scFv-Fc-IL-2 antibody-cytokine fusion protein that induces resting NK cells to highly efficient cytolysis of Hodgkin's lymphoma derived tumour cells.
abstract: The pathogenesis of Hodgkin's disease (HD) is associated with the accumulation of functionally anergic T cells in the near vicinity of the malignant Hodgkin/Reed-Sternberg (H/RS) cell. To stimulate locally the anti-tumour immunity in Hodgkin's disease, we generated an anti-CD30-antibody-interleukin-2 fusion protein (HRS3-scFv-Fc-IL-2) that binds to CD30 constitutively expressed on H/RS cells. The fusion protein is composed of a CD30 binding domain (HRS3-scFv) that is linked via the human IgG hinge-CH2/CH3 domain to human IL-2. The HRS3-scFv-Fc-IL-2 fusion protein is expressed as a 140 kDa homodimer, has binding specificities to both the CD30 antigen and the IL-2 receptor and stimulates proliferation of preactivated T cells in vitro, demonstrating its IL-2 bioactivity. After binding to CD30+ Hodgkin lymphoma cells, HRS3-scFv-Fc-IL-2 moreover induces resting NK cells, but not T cells, to lyse the lymphoma cells with high efficiency. Recruitment of resting NK cells towards a cytolytic immune response against CD30+ lymphoma cells has the potential to build up an effective anti-tumour response despite of Hodgkin's disease associated T-cell anergy and makes the HRS3-scFv-Fc-IL-2 fusion protein suitable for the specific immunotherapy of Hodgkin's lymphoma.
authors.affiliation: Klinik I für Innere Medizin, Labor Tumorgenetik, Universität zu Köln, and Center for Molecular Medicine Cologne, Köln, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Heuser
authors.forename: Stefan
authors.initials: S
authors.lastname: Guhlke
authors.forename: Alexander
authors.initials: A
authors.lastname: Matthies
authors.forename: Hans
authors.initials: H
authors.lastname: Bender
authors.forename: Stefan
authors.initials: S
authors.lastname: Barth
authors.forename: Volker
authors.initials: V
authors.lastname: Diehl
authors.forename: Hinrich
authors.initials: H
authors.lastname: Abken
authors.forename: Andreas
authors.initials: A
authors.lastname: Hombach
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D002469:Cell Separation; D016207:Cytokines / Q000737:chemistry*; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D006689:Hodgkin Disease / Q000378:metabolism*; D006801:Humans; D007128:Immunoglobulin Fragments / Q000737:chemistry*; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D019169:Jurkat Cells; D017730:Ki-1 Antigen / Q000096:biosynthesis* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D016207:Cytokines; D018076:DNA, Complementary; D007128:Immunoglobulin Fragments; D007376:Interleukin-2; D017730:Ki-1 Antigen; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins