Immunization with interleukin-2/interferon-?? double cytokine-secreting allogeneic fibroblasts prolongs the survival of mice with melanoma

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

“…Many reports have shown that combination therapies of cancer with two therapeutic genes are more effective than a therapy with one gene. Coexpression of IL-4/granulocyte-macrophage colony-stimulating factor, 25 IL-2/IL-12, 26 IL-2/interferon-␥, 27,28 or cytokine/ B7 29 by tumor cells or fibroblasts intensified antitumoral effects. Furthermore, the introduction of genes for both cytokines and suicide genes such as thymidine kinase or cytosine deaminase into tumor cells made the modified tumor cells sensitive to ganciclovir or 5-fluorocytosine and also activated antitumoral effector cell types by the secreted cytokines.…”

Cytokine immunogene therapy

“…In prior studies, immunity to melanoma and prolongation of survival was seen in mice with peripheral melanoma that were treated with allogeneic fibroblasts genetically engi-neered to secrete cytokines. 22,23 We found that in mice with an intracerebral malignant melanoma in which allogeneic fibroblasts genetically modified to secrete IL-2 were injected into the tumor bed, survival was significantly longer than that in untreated control mice injected with melanoma cells alone. 15 In these experiments, IL-2-secreting fibroblasts were cotransfected with genomic DNA from B16F1 melanoma cells to generate fibroblasts that secrete IL-2 and express melanoma-associated antigens (RLBA-IL-2).…”

Antigen-specific cytotoxicity and cell number of adoptively transferred T cells are efficiently maintainedin vivo by re-stimulation with an antigen/interleukin-2 fusion protein

“…The median survival time (MST) Ϯ SD of tumor-bearing mice in each group was determined by life-table methods and by log-rank analysis (Kim et al, 1995).…”