Attenuated mutant strain of Salmonella Typhimurium (STM) contrasts tumor growth and promotes antitumor immune patterns.

Introduction Cancer is the second cause of death in the western world and within a few years will become the leading one in developing countries (1). The incidence of cancer, as well as the biologic behavior, pathologic expression, and recognized risk factors, in pet population are similar to what is observed in humans (i.e. non-Hodgkin's lymphoma, prostate, head and neck, and mammary carcinoma, melanoma, soft tissue sarcoma, and osteosarcoma) (2). The use of conventional treatment modalities (surgical removal, chemo and radiotherapy) has considerable limitations, including toxicity, poor tumor targeting, inadequate tissue penetration, which together often result in incomplete destruction of the tumors. Therefore, prevention and control of cancer diseases is an important task for today’s medicine, due to either the possible implications of such diseases on public health or to their economic consequences. Therefore, the development of new therapeutic strategies to fight cancer is now a priority for research. In this regard, the use of bacteria as alternative cancer therapeutics, in particular their potential of bacteria to selectively target cancer cells has been studied for more than a century (3). Aims The aim of the study was to investigate the anti-cancer potential of an attenuated mutant strain of Salmonella Typhimurium (STM) devoid of the operon znuABC, coding for the high-affinity zinc transporter, which is important for the bacteria growth in environments poor in zinc and for the virulence of different gram-negative pathogens (4-6). Materials and methods 4T1 mammary adenocarcinoma cells were injected subcutaneously in immunocompetent Balb/c mice. Then, tumor and non-tumor bearing animals was injected or not (control) subcutaneously with STM. Tumor progression was monitored at different time points after treatment through size measurements and differences in mortality rates were observed among the groups. Phenotype and functional capacity of different immune parameters were explored by FACS and histological analysis of the peritumoral zone and spleen, and by assessing cytokine production through ELISA assay. Conclusions We showed that STM was able to penetrate and replicate into tumor cells in in vitro and in vivo models. The STM administration in mammary adenocarcinoma mouse model resulted in a significant reduction of tumor growth with a marked increase of life expectancy of STM treated mice. Finally, we provided evidence that STM promotes antitumor immune patterns, capable to influence clinical outcomes. On the whole, our results support the potential of STM as a promising anti-cancer therapy (5,6).