From aspecific to bispecific immunotherapy: immunomodulatory effects of interleukin-2 and T cell directed monoclonal antibodies in renal cell carcinoma patients

The aim of this study was to get more insight into the immunological effects of rIL-2 therapy in renal cell carcinoma patients. Special attention was given to the activation of T cells, since these cells appear to play an important role in the immune response against tumour cells. In addition, the immunological effects of the CD3 monoclonal antibody (MAb) OKT3 and the bispecific MAb BIS-1 were studied. The rationale for intravenous (iv) administration of OKT3 prior to IL-2 therapy was the in virro finding that this induces T cell activation. BIS-1 combines the specificities of the CD3 MAb RIV-9 and the MAb MOC31 directed against the carcinoma associated antigen EGP-2. The rationale for the iv administration of BIS-1 during IL-2 therapy was that BIS-1 could add specificity to IL-2 therapy and induce local T cell activation only at the site of the tumour. The immunological effects were studied by analysing the phenotypical and functional characteristics of peripheral blood lymphocytes before and during IL-2 therapy using flow cytometry, proliferation assays and ELISA. The results of this study may form a basis for further improvement of IL-2 based immunotherapy