Transcription Activator Reprogramming Gene Therapy (TARGET) of Breast Cancer Cells with Adenoviral Vectors for Interferon Regulatory Factors; Final rept. 15 Jul 2005-14 Jul 2006

摘要

Transcription factor reprogramming gene therapy of cancer results in upregulation of numerous genes which result in expression of numerous antitumor cytokines and chemokines as well as a host of proapoptotic proteins and other proteins that mediate cell death or terminal differentiation. This allows for the application of a single vector to achieve expression of a multitude of genes that could only be achieved by application of an impossibly large number of separate vectors. We have termed this concept as Transcription Activator Reprogramming GEne Therapy or TARGET. We and others have shown that certain Interferon Regulatory Factors upregulate numerous antitumor genes in cancer cells which results in expression of numerous cytokines chemokines and proapoptotic factors that result in a marked antitumor response both in terms of cell death and enhanced immune response against the cancer. We explored the concept that adenoviral vectors for IRF-3-3 can reprogram breast cancer cells to kill themselves resulting in eradication of the treated breast cancer cells by apoptosis.