1. Field of the Invention
The present invention relates generally to a novel microorganism strain, Salmonella typhimurium CRC2631, and it use as a cancer therapeutic.
2. Description of the Prior Art
The term ‘cancer’ refers generally to a condition in which cells in an organism undergo unchecked growth, tending toward limitless expansion and creation of a tumor. Cancer can originate anywhere in the human body. Cancers that arise from cells covering internal and external body surfaces are referred to as ‘carcinomas,’ while those developing from cells comprising the body's supportive tissues (such as fat, cartilage, bone, and the like) are called ‘sarcomas.’ Other categories of cancers include lymphomas and leukemias.
The unregulated growth of cancer cells is typically due to a mutation in the DNA of the cell, such as, for example, in genes controlling cell growth (e.g. the transformation of proto-oncogenes into oncogenes). In early stages, such mutations are not noticeable, and a cancer is typically discovered only after it has grown severe enough to produce symptoms in the patient. Early screening techniques can detect cancers prior to the onset of noticeable symptoms in the patient. Breast cancer, for example, is detectable in early stages by the use of mammography. Testing PSA levels in males, coupled with direct rectal exams, can allow a physician to detect early stages of prostate cancer. Early detection of a cancer significantly increases the likelihood of successful treatment of the patient.
A variety of treatment options exist for the cancer patient. For a male suffering from prostate cancer, for example, hormone-ablative therapy is often effective in treating the early stages of the disease. If the cancer progresses to an androgen-independent stage, other chemotherapies, such as the use of the compound taxol, are indicated. Patients can, however, develop resistance to chemotherapeutic agents such as taxol, and many chemotherapeutic agents are highly toxic to the body. Thus, alternative therapies are desired.
Salmonella is a genus of gram-negative, rod-shaped enterobacteria. The genus contains over 2,000 sero-species and is one of the most important pathogens in the Enterobacteriaceae family. They are facultative anaerobes, non-spore forming, and are usually motile, having peritrichous flagella. The organisms use citrate as a sole carbon source and typically ferment glucose, but not sucrose or lactose.
Taxonomically, all Salmonella fall into two species: S. enterica, and S. bongori, with six subspecies present. Popular species names, based largely on sero-typing, are commonly used. Salmonella are often referred to by genus and serovar, such as S. typhimurium, rather than by an extended nomenclature such as S. enterica subspecies enterica serovar typhimurium. For purposes of this document, the name S. typhimurium will be used to refer to S. enterica subspecies enterica serovar typhimurium. 
S. typhimurium is among the more common of the Salmonella serovars. The organism has a circular chromosome of approximately 4,857 kilobases (kb). It is known to cause salmonellosis in humans with varying degrees of severity. In some cases hospitalization is required. Clinical isolation of S. typhimurium is typically performed using MacConkey, XLD, XLT, DCA, or Önöz agars. Preliminary isolation generally requires a selective medium because of the presence of normal intestinal flora in the sample.
Salmonella-based therapies have been described with respect to prostate and breast cancers. Salmonella typhimurium strains, for example, have been found to target and destroy breast cancer and prostate cancer cells both in vitro and in animal models. S. typhimurium strain VNP20009, a Salmonella derived from strain ATCC14028, has been used in Phase I clinical trials for treatment of human cancers, but was found to have unacceptable levels of toxicity and was therefore unacceptable for use as a therapeutic organism.
What is needed, then, is a strain of S. typhimurium having reduced or no toxicity while retaining the ability to target and destroy cancer cells.