Cancer Immunotherapy Based on Killing of Salmonella-Infected Tumour Cells
Posted on: Thursday, 17 June 2004, 06:00 CDT
We have described a novel approach to cancer treatment that is based on the unique feature of invasive bacteria such as S. typhimurium to infect non-phagocytic cells. In fact we have shown that tumour cells are easily infected by invasive derivatives of S. typhimurium, through the expression of the type three secretion system. Infected tumour cells are not directly killed by S. Typhimurium. Rather, Salmonella-infected tumour cells upregulate the expression of MHC I molecules, present determinants of bacterial origin and become targets of anti-Salmonella specific T cells. Moreover, intratumoural injection of Salmonella facilitates the recruitment of immune cells into the infected tumour area, possibly explaining the intrinsic anticancer property reported in literature. In order to fully appreciate the anticancer therapeutic properties of invasive S. typhimurium, we expanded anti-Salmonella specific T cells through systemic vaccination just before topical bacterial application. In fact, we show here that the combination of intratumoural injection of invasive Salmonella with DC-based anti- Salmonella specific vaccination results in complete tumour regression in 60% of treated mice, whereas simple intratumoural bacterial injection leads to maximum 20% of survival. Furthermore, we have shown protective immunity to subsequent tumour challenge in nearly 80% of survived mice indicating the generation of specific responses to endogenously expressed tumour antigens. In conclusion, our combinatorial immuno-therapeutical approach helps overcome immune escape mechanisms adopted by tumour cells because it is independent on the kinetic of expression of tumour antigens and because it avoids ignorance of the tumour site.
F. Avogadri, C. Martinoli, L. Petrovska, C. Chiodoni, P. Transidico, M.P. Colombo, G. Dougan, M. Rescigno
European Institute of Oncology (IEO), Milan, Italy
Copyright Edizioni Minerva Medica Mar 2004
Related Articles
- Biology Of Emergent Salmonella Exposed
- Study Eliminating Cell Receptor Prevents Infection In Animals
- Eliminating Cell Receptor Prevents Infections in Animal Study
- Cancer Cells Revert to Normal at Specific Signal Threshold, Stanford Researchers Find
- ASCO Study Confirms Importance of Histology in Treatment of Non-Small Cell Lung Cancer With ALIMTA (Pemetrexed for Injection)
- Sangamo BioSciences Announces Breakthrough Results at ICAAC Demonstrating Protection of Cells From HIV Infection Following Treatment With Zinc Finger Nucleases
- Impact of the Liver-Specific Expression of SHIP2 (SH2-Containing Inositol 5'-Phosphatase 2) on Insulin Signaling and Glucose Metabolism in Mice
- Muscle-Specific Expression of IGF-1 Blocks Angiotensin II-Induced Skeletal Muscle Wasting
- Loss of Junctional Proteins is Not a Prerequisite for Tumour Cell Separation in Colon Cancer
 |
 |
User Comments (0)
RSS Feeds