Regulated Apoptosis and Immunogene Therapy for Prostate Cancer
Abstract
The central tenet of this proposal is that methods to effectively trigger apoptosis within prostate tumors can both reduce tumor burden and elicit adaptive immunity, provided a pro-inflammatory environment can be created. Previously created inducible caspases (iCaspases) have been used as the basis of both a prophylactic vaccine and as treatment of pre-existing subcutaneous (sc) and autochthonous TRAMP-derived prostate tumors. While these studies are centered on prostate cancer, they could be extended to other tumor types. The combination of iCaspases and IL-12 can completely eliminate small (less than or equal to 40 cu mm) sc tumors and largely eliminate larger (< 100 cu mm) tumors while IL-12 alone had minimal effect and iCaspase alone had no significant effect. Anti-tumor efficacy mirrored expansion of anti-tumor cytotoxic T lymphocytes and IFN-gamma-producing cells from splenocytes of vaccinated animals. Further, orthotopic injections into the prostates of tumor-bearing TRAMP mice trigger apoptosis, secondary necrosis and inflammation. Finally, in transgenic animals, the hK2-E3/P, PSA-E2/P and ARR2PB composite promoters are highly active in prostate epithelial cells and largely prostate specific. This work lays the groundwork for an "off-the-shelf" injectable immunogene therapy that could treat prostate cancer as a neoadjuvant therapy or possible less mutagenic treatment for metastatic disease.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2004
- Accession Number
- ADA427361
Entities
People
- David M. Spencer
Organizations
- Baylor College of Medicine