T-CELL ACTIVATION AND RETARGETING USING STAPHYLOCOCCAL-ENTEROTOXIN-B AND BISPECIFIC ANTIBODY - AN EFFECTIVE IN-VIVO ANTITUMOR STRATEGY

The aim of this work was to test for cure and immunity in a micrometas tatic tumor model using in vivo T cell activation with staphylococcal enterotoxin B (SEE) and retargeting with antitumor x anti-CD3 F(ab')(2 ) bispecific antibodies (bsAb). All studies were performed in C3H/HeN mice using syngeneic tumor cell lines. For survival studies, mice were injected intravenously on day 0 with CL62 (a p97-transfected clone of the K1735 murine melanoma tumor). Day-3 treatments included saline (c ontrol), SEE (50 gamma g intraperitoneal) with or without bsAb (5 mu g i.v.). Cured mice, surviving beyond 60 days, were rechallenged with s ubcutaneous CL62, K1735, or a nonmelanoma control, AG104. SEE activati on studies were performed with pulmonary tumor-infiltrating lymphocyte s isolated from 10-day established CL62 tumors. Maximal tumorinfiltrat ing lymphocyte cytotoxicity was demonstrated 24 h following SEE inject ion, therefore bsAb treatments were administered 24 h after SEE. When survival was examined at 60 days, there were significantly more surviv ors in the group receiving SEE plus bsAb (70%) compared to the group r eceiving SEE alone (30%), and the controls (0%) (P=0.02 and P<0.01, re spectively). Mice cured of CL62 using SEE alone or with bsAb demonstra ted equal immunity to CL62, however, mice treated with SEE plus bsAb w ere more often immune to the p97-parental cell line, K1735(P=0.001). A g104 consistently grew in all mice. Results of these studies demonstra te that SEE plus bsAb can be effective, not only in curing tumors but also in providing protective immunity against targeted and nontargeted tumor antigens.