Genetically engineered fibroblasts with antigen-presenting capability: Efficient induction of an antigen-specific cytotoxic T-lymphocyte response andprotection against tumor development in vivo

BLK mouse fibroblasts (H-2(b)) were genetically engineered to express costi mulatory B7.1 and interleukin-2 (BLK/IL2/B7.1). The BLK/IL2/B7.1 cells were then pulsed with an ovalbumin (OVA) epitope as a model antigen (Ag) (BLK/I L2/B7.1/OVA), and tested For the induction of OVA-specific cytotoxic T lymp hocytes (CTLs) in C57BL/6 mice (H-2(b)). The genetically engineered fibrobl asts lacking one or two of three factors (interleukin-2, B7.1, and OVA) wer e constructed and used as controls. Immunization with the BLK/IL2/B7.1/OVA cells induced strong cytotoxic activities against OVA-expressing EL4 (EG7) tumor cells, but not against other H-2(b) tumor cells, such as EL4, C1498 a nd B16F1 cells. The magnitude of the cytotoxic response in mice with the BL K/IL2/B7.1/OVA cells was significantly higher than the response in mice imm unized with any other cell constructs. CD8(+) T cells with OVA-specific cyt otoxic activities were predominant in mice immunized with the BLK/IL2/B7.1/ OVA cells. Furthermore, immunization with the BLK/IL2/B7.1/OVA cells signif icantly prolonged the survival of mice, compared with any other cell constr ucts, when the mice were challenged with EG7 tumor cells at 2 weeks postimm unization. Induction of antitumoral CTL immunity by the BLK/IL2/B7.1/OVA ce lls was independent of host Ag-presenting cells and of CD4(+) T-cell and na tural killer 1.1(+) cell help. These results suggest that fibroblasts can b e genetically modified to efficient Ag-presenting cells for the induction o f an Ag-specific CTL response.