IN-VIVO RETARGETING OF T-CELL EFFECTOR FUNCTION BY RECOMBINANT BISPECIFIC SINGLE-CHAIN FV (ANTI-CD3 X ANTIIDIOTYPE) INDUCES LONG-TERM SURVIVAL IN THE MURINE BCL1 LYMPHOMA MODEL

As demonstrated in several preclinical models, bispecific Abs are attr active immunotherapeutic agents for tumor treatment. We have previousl y reported that a bacterially produced anti-CD3 x antitumor bispecific single chain variable fragment of Ab fragment (BsscFv), which is capa ble of retargeting CTLs toward BCL1 tumor cells, exhibits antitumor ac tivity in vitro. To further facilitate BsscFv production, the coding s equence was subcloned in a eukaryotic expression vector and introduced into Chinese hamster ovary cells for large-scale production. In this report, we have determined the serum stability and the clearance rate from the circulation of BsscFv, Most important, we prove here the ther apeutic value of BsscFv in the treatment of BCL1 lymphoma, a murine mo del for human non-Hodgkin's lymphoma. Tumor-bearing mice that were tre ated with rscFv in combination with staphylococcal enterotoxin B super antigen, human rIL-2, or murine rIL-12 shelved long-term survival, whe reas untreated mice all died. This is the first report of the successf ul in vivo use of BsscFv as an immunotherapeutic agent. Furthermore, l ong-term survival was the result of complete tumor removal and was not due to the induction of dormancy.