Transcription factor Fos-related antigen 1 is an effective target for a breast cancer vaccine.

Abstract

Protection against breast cancer was achieved with a DNA vaccine against murine transcription factor Fos-related antigen 1, which is overexpressed in aggressively proliferating D2F2 murine breast carcinoma. Growth of primary s.c. tumor and dissemination of pulmonary metastases was markedly suppressed by this oral DNA vaccine, carried by attenuated Salmonella typhimurium, encoding murine Fos-related antigen 1, fused with mutant polyubiquitin, and cotransformed with secretory murine IL-18. The life span of 60% of vaccinated mice was tripled in the absence of detectable tumor growth after lethal tumor cell challenge. Immunological mechanisms involved activation of T, natural killer, and dendritic cells, as indicated by up-regulation of their activation markers and costimulatory molecules. Markedly increased specific target cell lysis was mediated by both MHC class I-restricted CD8+ T cells and natural killer cells isolated from splenocytes of vaccinated mice, including a significant release of proinflammatory cytokines IFN-gamma and IL-2. Importantly, fluorescence analysis of fibroblast growth factor 2 and tumor cell-induced vessel growth in Matrigel plugs demonstrated marked suppression of angiogenesis only in vaccinated animals. Taken together, this multifunctional DNA vaccine proved effective in protecting against growth and metastases of breast cancer by combining the action of immune effector cells with suppression of tumor angiogenesis.

• Authors: Yunping Luo, He Zhou, Masato Mizutani, Noriko Mizutani, Ralph A Reisfeld, Rong Xiang
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 100 Issue 15 Pg. 8850-5 (Jul 22 2003) ISSN: 0027-8424 [Print] United States
• PMID: 12857959 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Cancer Vaccines
• Interleukin-18
• Interleukin-2
• Proto-Oncogene Proteins c-fos
• Vaccines, DNA
• fos-related antigen 1
• Interferon-gamma

Topics

• Animals
• Cancer Vaccines (genetics, pharmacology)
• Dendritic Cells (immunology)
• Female
• Genetic Vectors
• In Vitro Techniques
• Interferon-gamma (biosynthesis)
• Interleukin-18 (genetics)
• Interleukin-2 (biosynthesis)
• Killer Cells, Natural (immunology)
• Lymphocyte Activation
• Mammary Neoplasms, Experimental (blood supply, genetics, immunology, prevention & control)
• Mice
• Mice, Inbred BALB C
• Neovascularization, Pathologic (prevention & control)
• Peyer's Patches (immunology)
• Proto-Oncogene Proteins c-fos (genetics, immunology)
• Salmonella typhimurium (genetics)
• T-Lymphocytes, Cytotoxic (immunology)
• Vaccines, DNA (genetics, pharmacology)