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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
Author(s) -
Heuser Claudia,
Guhlke Stefan,
Matthies Alexander,
Bender Hans,
Barth Stefan,
Diehl Volker,
Abken Hinrich,
Hombach Andreas
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20098
Subject(s) - cd30 , fusion protein , cytolysis , antibody , lymphoma , cytokine , biology , cancer research , immune system , antigen , interleukin 2 , immunology , immunotherapy , microbiology and biotechnology , in vitro , cytotoxicity , recombinant dna , biochemistry , gene
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. © 2004 Wiley‐Liss, Inc.