| First Author | Nanni P | Year | 1998 |
| Journal | Cancer Res | Volume | 58 |
| Issue | 6 | Pages | 1225-30 |
| PubMed ID | 9515809 | Mgi Jnum | J:46416 |
| Mgi Id | MGI:1197833 | Citation | Nanni P, et al. (1998) Interleukin 12 gene therapy of MHC-negative murine melanoma metastases. Cancer Res 58(6):1225-30 |
| abstractText | Immunological gene therapy of cancer relies heavily on the activation of T cells, but tumors with defects in MHC gene expression are not recognized by MHC-restricted T cells. To investigate the potential of cytokine genes for the therapy of MHC-negative tumors, we transduced B78H1, a class I-negative murine melanoma clone, with a polycistronic vector carrying murine interleukin (IL)-12 genes. The clones studied produced 400-25,000 pg/ml IL-12; their in vitro growth properties were similar to those of parental cells. A complete inhibition of growth was observed in vivo both after s.c. and i.v. administration of all IL-12 clones. IL-12-transduced cells were also used as a therapeutic vaccine in mice bearing micrometastases by nontransduced parental cells. A significant (80-90%) reduction in the number of lung nodules was obtained. Immunohistochemical analysis and studies in immunocompromised hosts showed that T cells and natural killer cells had a significant role in the elimination of IL-12-releasing cells. In situ hybridization with cytokine probes detected a strong increase in the proportion of leukocytes positive for IFN-gamma, tumor necrosis factor alpha, IL- 1beta, and IFN-inducible protein 10 at the site of rejection of IL-12 engineered tumor cells. However, it was clear that the loss of in vivo growth was also due to T-cell- and natural killer cell-independent factors, possibly related to the antiangiogenic properties of IL-12. In conclusion, tumor therapy based on IL-12 gene transduction was effective on a MHC-negative metastatic tumor, suggesting a possible application to MHC-defective human neoplasms. |
