Augmentation of antitumor immunity by genetically engineered fibroblast cells to express both B7.1 and interleukin-7

Mouse fibroblasts (H-2(b)) were genetically engineered to express a costimu latory B7.1 and an interleukin-7 (IL-7; Fb/B7.1/IL7). The Fb/B7.1/IL7 cells were then pulsed with an ovalbumin (OVA) epitope (amino acids 257-264, SII NFEKL, H-2 K-b restricted; Fb/B7.1/IL7/OVA) and tested for the induction of OVA-specific cytotoxic T lymphocytes (CTLs) in C57BL/6 mice (H-2(b)). The genetically engineered fibroblasts lacking either B7.1 or IL-7 were constru cted and used as controls. Immunization with the Fb/B7.1/IL7/OVA cells indu ced strong cytotoxic activities against OVA-expressing EL4 (EG7) tumor cell s. The magnitude of the cytotoxic response in mice with the Fb/B7.1/IL7/OVA cells was significantly higher than the response in mice immunized with an y other cell constructs. CD8(+) T cells were a major effector cell-type of antitumor response in the immunized mice with the Fb/B7.1/IL7/OVA cells. Fu rthermore, immunization with the Fb/B7.1/IL7/OVA cells significantly prolon ged the survival period of mice when the mice were injected with EG7 tumor cells one week after the immunization. These results suggest that fibroblas ts can be genetically modified to an efficient cell vaccine for the inducti on of antitumor response. (C) 2000 Published by Elsevier Science Ltd. All r ights reserved.