PROJECT STEALTH UPDATE
December 15, 2014
Overall, in the last 6 months, our research lab has submitted 2 manuscripts and all have been accepted for publication. They are as follows:
1. Michael J. Mertensotto, Jeremy J. Drees, Lance B. Augustin, Janet L. Schottel, Daniel A. Saltzman: Increased Expression of Periplasmic Chaperones in Salmonella Typhimurium Reduces Its Viability In Vivo Current Microbiology, Nov, 2014.
2. Drees J, Mertensotto M, Liu G, Panyam, J, Augustin L, Schottel J, and Saltzman D: Attenuated Salmonella enterica Typhimurium Reduces Tumor Burden in an Autochthonous Breast Cancer Model. Anticancer Research, In Press, 2015
As you recall, our research centers on the fact that Salmonella finds, attaches itself, and colonizes solid cancers and we then use this unique property to deliver a host of immune modulating proteins to alter the tumor micro-environment to facilitate an immune mediated tumor destruction. Our work is now focused on 2 particular cancer models. First we are studying our treatment strategy in a mouse model of triple negative breast cancer and second in mice who posses a breast cancer gene in that these animals spontaneously develop breast cancer. It is now the opinion of many cancer researchers that the ideal and most “true to life” way to study potential cancer treatments are in animal models where the animal will spontaneously develop a cancer and not in a model where a researcher gives an animal a cancer and then treats this cancer 2 weeks later.
Over the last 6 months, we have concentrated our efforts in finding the most ideal strain of Salmonella that colonizes cancers the best. Not all strains are equal and we have discovered that strain SL3261 of Salmonella is the best at tumor invasion and colonization.
In the above figure, one can notice a nearly 4 fold better in tumor colonization after a single dose of Salmonella in mice with breast cancer. Subsequent efforts in the laboratory were then centered on genetically engineering this SL3261 strain of Salmonella to carry the various immune modulating proteins that our previously studied strains carried. Current laboratory efforts are now using this optimum tumor colonizing strain of Salmonella in the breast cancer models in mice. The following graph illustrates 3 cohorts of mice; control animals, mice given salmonella without any immune altering proteins and mice given salmonella with a combination of 4 immune modulating proteins. This preliminary study illustrates that administration of the salmonella with the immune modulating proteins not only prevents tumor growth but actual regression.
Currently, our efforts are now concentrated on optimizing the timing of the dosing and strategies to further increase tumor colonization. One of the strategies we are using to enhance tumor invasion and colonization is a medication called a vascular disrupting agent or VDA. Experiments conducted in our laboratory demonstrated a nearly 1000 time better tumor invasion by Salmonella when these VDA’s are used.
Again, thank you very much for your generous support of our research lab at the University of Minnesota.
Daniel Saltzman, M.D., PhD.
Associate Professor of Surgery and Pediatrics
Chief, Division of Pediatric Surgery
Surgeon-in-Chief, University of Minnesota Masonic Children’s Hospital