Induction of antitumor immunity after cure of pulmonary metastases, using staphylococcal enterotoxin B and bispecific antibody

The combination of staphylococcal enterotoxin B (SEB) and anti-p97 x anti-C D3 bispecific antibody (bsAb) cures 60%-80% of mice with established pulmon ary metastases of the syngeneic p97(+) murine melanoma, CL62. We investigat ed the ability of cured mice to generate protective antitumor immunity. In tumor rechallenge experiments, CL62-cured mice developed protective immunit y against rechallenge with CL62. The majority of mice also rejected the p97 -negative parental cell line, K1735, indicating an immune response to tumor antigens common to both cell lines that were not bsab-targeted. A signific ant humoral response developed against p97 antigen, but not against other a ntigens common to both CL62 and K1735. That the majority of cured mice neve rtheless rejected K1735 suggests that tumor immunity is not antibody-depend ent. Evidence of cellular immunity was obtained from the results of delayed -type hypersensitivity, proliferation and cytotoxicity assays, which reveal ed the presence of tumor-specific memory in bsAb-treated, CL62-cured mice. CD8(+) T cells from cured, but not control mice were able to lyse tumor; ho wever, memory CD4 cells had no cytolytic function. In vivo, however, both C D4 and CD8 T cells were required for effective protective immunity. These s tudies demonstrate that treatment with SEB and bsAb not only confers passiv e immune effects of tumor eradication, but also actively promotes the gener ation of a host antitumor immune response.