A potent, imaging adenoviral vector driven by the cancer-selective mucin-1 promoter that targets breast cancer metastasis.
OBJECTIVE
With breast cancer, early detection and proper staging are critical, and will often influence both the treatment regimen and the therapeutic outcome for those affected with this disease. Improvements in these areas will play a profound role in reducing mortality from breast cancer.


METHODS
In this work we developed a breast cancer-targeted serotype 5 adenoviral vector, utilizing the tumor-specific mucin-1 promoter in combination with the two-step transcriptional amplification system, a system used to augment the activity of weak tissue-specific promoters.


RESULTS
We showed the strong specificity of this tumor-selective adenovirus to express the luciferase optical imaging gene, leading to diagnostic signals that enabled detection of sentinel lymph node metastasis of breast cancer. Furthermore, we were able to target hepatic metastases following systemic administration of this mucin-1 selective virus.


CONCLUSIONS
Collectively, we showed that the amplified mucin-1 promoter-driven vector is able to deliver to and selectively express a desirable transgene in metastatic lesions of breast tumors. This work has strong clinical relevance to current diagnostic staging approaches, and could add to targeted therapeutic strategies to advance the fight against breast cancer.
Department of Molecular and Medical Pharmacology, University of California at Los Angeles School of Medicine, Los Angeles, California, USA.
Steven T
ST
Huyn
Jeremy B
JB
Burton
Makoto
M
Sato
Michael
M
Carey
Sanjiv S
SS
Gambhir
Lily
L
Wu
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D003587:Cytomegalovirus / Q000235:genetics; D003952:Diagnostic Imaging; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008113:Liver Neoplasms / Q000175:diagnosis / Q000556:secondary / Q000628:therapy*; D008156:Luciferases / Q000378:metabolism; D008207:Lymphatic Metastasis; D051379:Mice; D016513:Mice, SCID; D018396:Mucin-1 / Q000235:genetics*; D049268:Positron-Emission Tomography; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014057:Tomography, X-Ray Computed; D019076:Transgenes / Q000502:physiology; D014407:Tumor Cells, Cultured
D018396:Mucin-1; D008156:Luciferases