Activation of resting T cells against the CA 72-4 tumor antigen with an anti-CD3/CA 72-4 bispecific antibody in combination with a costimulatory anti-CD28 antibody.

The poor prognosis of advanced gastric carcinoma requires new therapeutic approaches. Among these, the specific activation of resting lymphocytes by bispecific antibodies may be promising. Here we describe the generation and function of a bispecific monoclonal antibody (bi-mab) with specificity for CD3 and for the tumor antigen CA72-4 (TAG72) on various gastrointestinal tumors. We established a hybrid/hybridoma by somatic fusion of two hybridoma lines secreting antibodies against CA72-4 and CD3 respectively and characterized its bimab OKT3/B72.3. In combination with costimulatory anti-CD28 antibodies resting peripheral lymphocytes could be activated specifically by bi-mab OKT3/B72.3 with T cell proliferation and IL-2 secretion. The bi-mab OKT3/B72.3 could also trigger the cytotoxicity of these T cells toward, CA72-4+ cells in vitro. Our results indicate, that bi-mab OKT3/B72.3 in combination with an anti-CD28 mab can redirect T cell cytotoxicity specifically against CA72-4+ tumor cells implicating a novel strategy for the specific immunotherapy of CA72-4+ tumors.