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: Anna R Kwilas, Andressa Ardiani, Ulrike Dirmeier, Cornelia Wottawah, Jeffery Schlom, James W Hodge
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 29 Pg. 28194-210 (Sep 29 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 26317648 (Publication Type: Journal Article)

Chemical References

• Cancer Vaccines
• Twist-Related Protein 1
• Vaccines, Synthetic
• rV-Tricom

Topics

• Animals
• CD4-Positive T-Lymphocytes (drug effects, immunology, metabolism)
• CD8-Positive T-Lymphocytes (drug effects, immunology, metabolism)
• Cancer Vaccines (genetics, immunology, metabolism)
• Cell Line, Tumor
• Female
• Gene Expression Regulation, Neoplastic (immunology)
• Male
• Mammary Neoplasms, Animal (genetics, immunology, prevention & control)
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Transgenic
• Neoplasm Metastasis
• Prostatic Neoplasms (genetics, immunology, prevention & control)
• Reverse Transcriptase Polymerase Chain Reaction
• Survival Analysis
• Treatment Outcome
• Tumor Burden (drug effects, genetics, immunology)
• Twist-Related Protein 1 (genetics, immunology, metabolism)
• Vaccination
• Vaccines, Synthetic (genetics, immunology, metabolism)
• Vaccinia virus (genetics, immunology, metabolism)