Simultaneous targeting of IL2 and IL12 to Hodgkin's lymphoma cells enhances activation of resting NK cells and tumor cell lysis.
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.
Hombach
Andreas
A
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
Heuser
Claudia
C
Abken
Hinrich
H
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
D007128:Immunoglobulin Fragments; D007376:Interleukin-2; D017730:Ki-1 Antigen; D011993:Recombinant Fusion Proteins; D018664:Interleukin-12; D007371:Interferon-gamma