IMMUNOMODULATORY EFFECTS OF INTRAVENOUS BIS-1 F(AB')(2) ADMINISTRATION IN RENAL-CELL CANCER-PATIENTS

We report the immunomodulatory effects of an intravenous treatment wit h F(ab')(2) fragments of the bispecific monoclonal antibody BIS-1 duri ng subcutaneous recombinant interleukin 2 (rIL-2) therapy of renal cel l cancer (RCC) patients. BIS-1 is directed against both the CD3 antige n on T cells and the EGP-2 molecule on carcinoma cells and some normal epithelia. The amount of BIS-1 F(ab')(2) bound to peripheral blood ly mphocytes (PBLs) increased dose-dependently. This occupation degree wa s highest at the end of the 2 h infusion and rapidly decreased subsequ ently. During the first hour of BIS-1 F(ab')(2) infusion the number of PBLs decreased slowly. This was followed by an increase in serum tumo ur necrosis factor alpha (TNF-alpha) concentrations and a rapid decrea se in the numbers of peripheral blood lymphocytes, monocytes and eosin ophils. In our view, the most likely explanation for the observed decr ease in occupation degree of BIS-1 F(ab')(2) and the rise in TNF-alpha levels is based on the assumption that BIS-1-carrying T cells leave t he circulation. The CD3 antigens on these extravasated T cells become cross-linked by EGP-2 antigens, inducing TNF-alpha secretion. This res ults in an enhanced decrease in the numbers of PBLs, monocytes and eos inophils. These preliminary results suggest that BIS-1 F(ab')(2) treat ment during IL-2 therapy may induce local T-cell activation.