Ts. Kim et al., Therapeutic anti-tumor response induced with epitope-pulsed fibroblasts genetically engineered for B7.1 expression and IFN-gamma secretion, INT J CANC, 87(3), 2000, pp. 427-433
Mouse fibroblasts (H-2(b)) were genetically engineered to express a co-stim
ulatory B7.1 and an IFN-gamma (Fb/IFN-gamma/B7.1). The Fb/IFN-gamma/B7.1 ce
lls were then pulsed with an ovalbumin epitope (amino acids 257-264, SIINFE
KL, H-2K(b)-restricted) as a model antigen (Fb/IFN-gamma/B7.1/OVA) and test
ed for the induction of OVA-specific cytotoxic T lymphocytes (CTLs) in C57B
L/6 mice (H-2(b)). Genetically engineered fibroblasts lacking either IFN-ga
mma or B7.1 were constructed and used as controls. Immunization with the Fb
/IFN-gamma/B7.1/OVA cells induced strong cytotoxic activity against OVA-exp
ressing EL4 (EG7) tumor cells but not: against other H-2(b) tumor cells, su
ch as EL4, C1498, and B16F1. The magnitude of the cytotoxic response in mic
e with the Fb/IFN-gamma/B7.1/OVA cells was significantly higher than that i
n mice immunized with any other cell construct, CD8(+) T cells with OVA-spe
cific cytotoxic activity were predominant in mice immunized with Fb/IFN-gam
ma/B7.1/OVA cells. Furthermore, treatment with Fb/IFN-gamma/B7.1/OVA cells
significantly prolonged the survival period of EG7 tumor-bearing mice. Anti
-tumor CTL immunity by the Fb/IFN-gamma/B7.1/OVA cells could be induced wit
hout the help of host antigen-presenting cells, CD4(+) T cells, or NK1.1(+)
cells. Our results suggest that fibroblasts can be genetically modified in
to efficient antigen-presenting cells for the induction of antigen-specific
CTL response in cancer immunotherapy. Int. J. Cancer 87:427-433, 2000. (C)
2000 Wiley-Liss, Inc.