A BISPECIFIC ANTIBODY PROLONGS SURVIVAL IN MICE BEARING LUNG METASTASES OF SYNGENEIC MAMMARY ADENOCARCINOMA

In the present study we tested whether T cells retargeted with a bispe cific antibody (bsAb) could block the growth of lung metastases of syn geneic mammary adenocarcinoma in immunocompetent mice. BALB/c mice wer e injected i.v. with tumor and i.p. with a genetically engineered bisp ecific F(ab')(2) [bs(Fab')(2)] having specificity for murine CD3 epsil on chain and for the gp52 mouse mammary tumor viral glycoprotein, whic h is expressed on the tumor cells. The bs(Fab')(2) was physically stab le in blood and serum, was removed from the body with a half-time of 1 2-15 h, and accumulated in lymphoid tissue where it bound to T cells. We show that treatment of tumor bearing mice with the bs(fab')(2) sign ificantly prolonged their survival relative to untreated controls. Two other genetically engineered bs(fab')(2)s having specificity for muri ne CD3 epsilon chain and irrelevant antigens did not inhibit tumor gro wth. In addition, survival was not affected by bsAb therapy using a va riant tumor cell line that expressed low levels of the gp52 target ant igen. Inhibition of tumor growth was even more evident by histologic a nalysis. Treatment with the relevant bs(fab')(2) resulted in a marked reduction of tumor burden in lung sections taken on days 7, 9 and 11. This is the first report demonstrating that a bsAb can inhibit the gro wth of syngeneic solid tumor metastases in mice without addition of T cell activators.