Our research in 2011 builds on our hard work and success of previous years as we continue the maturation of our bacterial cancer targeting (BCT) therapy.  Our genetically modified, non-pathogenic Salmonella specifically targets and persists in tumors but not normal cell lines. We are identifying and improving mechanisms by which Salmonella targets tumors while engineering Salmonella to efficiently destroy tumors with minimal side effects.

Salmonella target and kill tumor cells directly and are being further genetically modified to serve as a delivery vehicle for cancer therapies that cannot specifically target tumors.  When targeted to the cancer site, this BCT combination therapy will destroy tumors with maximum efficiency but minimal side effects. Our goal is to tailor the best match of combination therapy to the tumor’s genetic profile – choosing the right therapeutic components that have demonstrated to most efficiently destroy the tumor being targeted.

We are in the process of testing new anti-cancer compounds produced by the bacteria at the cancer site, as well as attaching molecular scaffolds on the surface of the bacteria that can be used to shuttle large numbers of nanoparticles and other therapeutic drugs to the cancer site.  These scaffolds can also be used to enhance the tumor targeting specificity of our bacteria.

Continued work on our animal models demonstrates the safety of our BCT therapy.  We have established that our therapy can be taken on a regular basis in our prostate cancer mouse models without adverse reactions from the immune system, an important step towards bringing BCT therapy into the clinic. In 2011 we are testing clinical doses of BCT therapy in both mice with prostate tumors and rats with breast tumors in order to determine how much therapeutic Salmonella is needed to cure and significantly extend the life span of these animals. Currently, these animals live less than one year due to their tumor development.  Our goal is to have them live as long as mice and rats that do not develop tumors.

We are pursuing collaborations with other cancer-fighting organizations including local organizations (Immunophotonics, Inc. and the University of Missouri – Columbia) as well as scientific collaborations with colleagues in California, Australia and China.  By combining our therapeutic efforts, we can see if our anti-cancer treatments are stronger when used together rather than alone.  All these efforts bring BCT therapy another step closer to successful clinical use.

Dr. Robert A. Kazmierczak
Senior Investigator, Cancer Research Center

Starting in the late 1940âs, Miloslav Demerec and associates at Cold Spring Harbor Laboratory and Brookhaven National Laboratory stocked an extensive collection of auxotrophic mutants for the purpose of mapping the S. typhimurium LT2 chromosome. Over 10,000 of these original sealed agar stab cultures (0.5 ml/agar stab vial) are now curated in our laboratory at the Cancer Research Center. Information on alleles is from labels on vials or from original notebooks.

Determination of the Role of Estrogen in Colon Cancer Development Using Estrogen Receptors in Knock Out Mice

Prostate cancer occurs in a latent or clinical form in 30-40% of men by age 40-50, increasing substantially in men over 50 years of age. Current use of drugs and radiation has been partially effective only when the cancer is diagnosed early. Thus, research is needed into novel approaches to cure this devastating disease. The Cancer Research Center’s (CRC) novel approach utilizes a therapeutic strain of Salmonella typhimurium (CRC2631) to selectively target and destroy prostate tumor cells.

In this strategy, developed at the University of Missouri, drugs are linked up with radioactive metals that specifically attach to tumor cells. First, this can provide a visual image to pinpoint the tumor. Next, the energy emitted from the radioactive metal can then destroy tumor cells.

Cancers all have one thing in common. All tumors are initiated by damage to DNA. Fortunately, cells have repair mechanisms for repair of this damage. However, in some cases, damages is too great or repair is inadequate, thus cancer develops.

Chemical and Biochemical Reactions of Dithiolethiones in Certain Foods