T-helper- and accessory-cell-independent cytotoxic responses to human tumor cells transfected with A B7 retroviral vector



As a means to increase the immunogenicity of tumor cells, we have developed a retroviral vector to transfect human B7, a molecule capable of delivering co-stimulatory signals to T cells. Three different tumors, a melanoma, an ovarian carcinoma and a myelomonocytic leukemia, were transfected with high efficiency. When compared for their capacity to stimulate allogeneic T cells, B7+ but not B7 tumor cells were able to stimulate strong proliferative and cytotoxic responses. The effector CTL generated recognised B7+ and B7 cells as well as untransfected tumor cells, indicating that B7 is required in the inductive but not the effector phase of the response. Remarkably, B7+ tumor cells were able to induce cytotoxic responses both by CD4-depleted and by CD8-purified T cells, demonstrating that expression of B7 is at the same time necessary and sufficient to induce a cytotoxic response in the absence of T-helper cells and accessory cells.