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 costimulatory 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, SIINFEKL, 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 constructed and used as controls. Immunization with the Fb/B7.1/IL7/OVA cells induced strong cytotoxic activities against OVA-expressing EL4 (EG7) tumor cells. 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 any 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. Furthermore, immunization with the Fb/B7.1/IL7/OVA cells significantly prolonged the survival period of mice when the mice were injected with EG7 tumor cells one week after the immunization. These results suggest that fibroblasts can be genetically modified to an efficient cell vaccine for the induction of antitumor response.
Kim
T S
TS
College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Kwangju, South Korea. taekim@chonnam.chonnam.ac.kr
Chung
S W
SW
Hwang
S Y
SY
D000276:Adjuvants, Immunologic / Q000235:genetics*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000235:genetics; D016827:CD8 Antigens / Q000276:immunology; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000276:immunology* / Q000378:metabolism*; D005818:Genetic Engineering; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D015851:Interleukin-7 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D016019:Survival Analysis; D013945:Thymoma / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000637:transplantation
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D016827:CD8 Antigens; D018076:DNA, Complementary; D015851:Interleukin-7; D010047:Ovalbumin