T-HELPER-CELL-INDEPENDENT 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 response. 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. (C) 1994 Wiley-Liss, Inc.