Therapeutic anti‐tumor response induced with epitope‐pulsed fibroblasts genetically engineered for B7.1 expression and IFN‐γ secretion

Mouse fibroblasts (H‐2b) were genetically engineered to express a co‐stimulatory B7.1 and an IFN‐γ (Fb/IFN‐γ/B7.1). The Fb/IFN‐γ/B7.1 cells were then pulsed with an ovalbumin epitope (amino acids 257–264, SIINFEKL, H‐2Kb‐restricted) as a model antigen (Fb/IFN‐γ/B7.1/OVA) and tested for the induction of OVA‐specific cytotoxic T lymphocytes (CTLs) in C57BL/6 mice (H‐2b). Genetically engineered fibroblasts lacking either IFN‐γ or B7.1 were constructed and used as controls. Immunization with the Fb/IFN‐γ/B7.1/OVA cells induced strong cytotoxic activity against OVA‐expressing EL4 (EG7) tumor cells but not against other H‐2b tumor cells, such as EL4, C1498, and B16F1. The magnitude of the cytotoxic response in mice with the Fb/IFN‐γ/B7.1/OVA cells was significantly higher than that in mice immunized with any other cell construct. CD8+ T cells with OVA‐specific cytotoxic activity were predominant in mice immunized with Fb/IFN‐γ/B7.1/OVA cells. Furthermore, treatment with Fb/IFN‐γ/B7.1/OVA cells significantly prolonged the survival period of EG7 tumor‐bearing mice. Anti‐tumor CTL immunity by the Fb/IFN‐γ/B7.1/OVA cells could be induced without the help of host antigen‐presenting cells, CD4+ T cells, or NK1.1+ cells. Our results suggest that fibroblasts can be genetically modified into efficient antigen‐presenting cells for the induction of antigen‐specific CTL response in cancer immunotherapy. Int. J. Cancer 87:427–433, 2000. © 2000 Wiley‐Liss, Inc.

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