title: A poxviral-based cancer vaccine the transcription factor twist inhibits primary tumor growth and metastases in a model of metastatic breast cancer and improves survival in a spontaneous prostate cancer model.
abstract: Several transcription factors play a role in the alteration of gene expression that occurs during cancer metastasis. Twist expression has been shown to be associated with the hallmarks of the metastatic process, as well as poor prognosis and drug resistance in many tumor types. However, primarily due to their location within the cell and the lack of a hydrophobic groove required for drug attachment, transcription factors such as Twist are difficult to target with conventional therapies. An alternative therapeutic strategy is a vaccine comprised of a Modified vaccinia Ankara (MVA), incorporating the Twist transgene and a TRIad of COstimulatory Molecules (B7-1, ICAM-1, LFA-3; TRICOM). Here we characterize an MVA-TWIST/TRICOM vaccine that induced both CD4+ and CD8+ Twist-specific T-cell responses in vivo. In addition, administration of this vaccine reduced both the primary tumor growth and metastasis in the 4T1 model of metastatic breast cancer. In the TRAMP transgenic model of spontaneous prostate cancer, MVA-TWIST/TRICOM alone significantly improved survival, and when combined with the androgen receptor antagonist enzalutamide, the vaccine further improved survival. These studies thus provide a rationale for the use of active immunotherapy targeting transcription factors involved in the metastatic process and for the combination of cancer vaccines with androgen deprivation.
authors: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors: Anna R
authors: AR
authors: Kwilas
authors: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors: Andressa
authors: A
authors: Ardiani
authors: Bavarian Nordic, Martinsried, Germany and Mountain View, CA, USA.
authors: Ulrike
authors: U
authors: Dirmeier
authors: Bavarian Nordic, Martinsried, Germany and Mountain View, CA, USA.
authors: Cornelia
authors: C
authors: Wottawah
authors: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors: Jeffery
authors: J
authors: Schlom
authors: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors: James W
authors: JW
authors: Hodge
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D019496:Cancer Vaccines; D051879:Twist-Related Protein 1; D014614:Vaccines, Synthetic; C439566:rV-Tricom
keywords: TRICOM; Twist; immunotherapy; metastasis; vaccine