Heterogeneous interleukin-15 inducibilities in murine B16 melanoma and RM-1 prostate carcinoma by interferon-alpha treatment.

Abstract

Long-term treatment of mouse cancer cells with interferon-alpha (IFN-alpha) converts parental B16 melanoma cells to B16alpha vaccine cells. Inoculation of syngeneic mice with UV-irradiated B16alpha vaccine cells triggers immunity to the parental B16 tumor that is mediated by host macrophages, T cells, and NK cells. Lymph node cells from mice inoculated with irradiated B16alpha vaccine cells, but not with irradiated parental cells, proliferate when cultured in vitro, suggesting long-term in vivo activation of lymphoid cells. Both IL-15 mRNA and IL-15 protein are highly induced in B16alpha vaccine cells. The bulk of the induced IL-15 is shown to be cell-associated, either cytoplasmic or membranous. The current study investigated the feasibility of applying the B16alpha vaccination protocol to generate a cancer vaccine against murine RM-1 prostate carcinoma. In comparison to B16alpha vaccine cells, long-term IFN-alpha-treated RM-1 cells (RM-1alpha vaccine cells) showed significant IL-15 mRNA induction but relatively low IL-15 protein up-regulation. When UV-irradiated, a 3-fold increase in intracellular IL-15 was observed in RM-1alpha vaccine cells, suggesting UV damage may have negated a possible control mechanism for IL-15 synthesis. Efficacy of in vivo vaccination of syngeneic mice with UV-irradiated RM-1alpha and B16alpha vaccine cells showed correlation between high IL-15 level and high vaccine efficacy in B16alpha cells compared to low IL-15 level and low vaccine efficacy in RM-1alpha cells. This supports the concept that the induction of IL-15 in tumor cells can be useful for creating whole-cell cancer vaccines.

• Authors: Tzu G Wu, Joana R Perdigão, Theresa K Umhoefer, Jade Cao, David A Ansari, Thomas B Albrecht, Eugene P Knutson, William A Rose 2nd, Angela J Jorgensen, Lee M Ryan, Linda E Abdalla, William Robert Fleischmann Jr
• Journal: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research (J Interferon Cytokine Res) Vol. 29 Issue 11 Pg. 719-28 (Nov 2009) ISSN: 1557-7465 [Electronic] United States
• PMID: 19642895 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Cancer Vaccines
• Interferon-alpha
• Interleukin-15
• RNA, Messenger

Topics

• Animals
• Cancer Vaccines
• Carcinoma (immunology, pathology, prevention & control)
• Interferon-alpha (immunology, metabolism)
• Interleukin-15 (biosynthesis, genetics, immunology)
• Lymphocyte Activation
• Male
• Melanoma, Experimental (genetics, immunology, pathology, prevention & control)
• Mice
• Mice, Inbred C57BL
• Neoplasm Transplantation
• Prostatic Neoplasms (genetics, immunology, pathology, prevention & control)
• Protein Biosynthesis (immunology)
• RNA, Messenger (analysis)
• Transcriptional Activation (immunology)