Secretion of Biologically Active Superantigens by Mammalian Cells

Abstract

The genetic modification of tumor cells to secrete immune regulatory molecules can elicit a potent antitumor immune response. Bacterial superantigens are among the most potent T cell mitogens. Activation of tumor-sensitized T cells by bacterial superantigens can lead to immune effector cells with potent and specific in vivo antitumor activity. Retrovirus vectors encoding for the bacterial superantigens SEA and SEC2 were constructed, and recombinant retrovirus stocks were generated. SEA and SEC2 could be detected in the culture supernatant of tumor cells after a single exposure to retrovirus. Molecular analysis of the genetically modified cells revealed intact proviral DNA and abundant vector-derived superantigen RNA. Biologic activity was apparent for both superantigens. Secretion of biologically active superantigen by mammalian cells has not been reported previously, and this will enable investigating the potential for superantigen gene therapy.