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

作者：Heuser C; Guhlke S; Matthies A; Bender H; Barth S; Diehl V; Abken H; Hombach A^*

来源：International Journal of Cancer, 2004, 110(3): 386-394.

DOI：10.1002/ijc.20098

• recombinant antibodies
• scFv
• antibody-cytokine-fusion protein
• IL-2 fusion protein
• immunotherapy

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.

• 出版日期2004-6-20