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.
Döhring
C
C
Basel Institute for Immunology, Switzerland.
Angman
L
L
Spagnoli
G
G
Lanzavecchia
A
A
D000938:Antigen-Presenting Cells / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D003602:Cytotoxicity, Immunologic; D017931:DNA Primers / Q000737:chemistry; D005822:Genetic Vectors; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000628:therapy; D012190:Retroviridae; D013601:T-Lymphocytes / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
D018122:B7-1 Antigen; D017931:DNA Primers