Design of Salmonella Based Vaccines for Cancer

Attenuated microorganisms have emerged as candidates for a novel anti-cancer approach in which they enhance anti-cancer immunity by boosting the innate immune system. Salmonella-based therapeutic vaccines are an attractive and novel alternative for conventional cancer treatment. Creative Biolabs is a world leader in the field of cancer vaccine development. With our extensive experience and advanced platform, we are therefore confident in offering the best development services for Salmonella-based vaccines. We guarantee the finest results for our customers all over the world.

The design of efficient vectors for vaccine development and cancer gene therapy is an area of intensive research. Bacteria-based vectors are being investigated as optimal vehicles for antigen and therapeutic gene delivery to immune and tumour cells. Attenuated Salmonella strains have shown great potential as live vectors with broad applications in human and veterinary medicine. An impressively high, and still growing, number of reports published over the last two decades have demonstrated the effectiveness in animal models of Salmonella-based therapies for the prevention and treatment of infectious and non-infectious diseases, as well as cancer. Further, the recent dramatic expansion in knowledge of genetics, biology, and pathogenesis of the bacteria allows more rational design of Salmonella constructs tailored for specific applications.

Salmonella

Salmonella belongs to the Enterobactericae family, a group of Gram-negative, facultatively anaerobic and facultatively intracellular pathogenic bacteria. Currently, based on genome sequence similarity, the genus Salmonella is categorized into two species S. bongori and S. enterica which in turn is divided into six subspecies including S. enterica subsp. enterica.

Salmonella sp. has an ability to multiply inside phagocytic and nonphagocytic cells including macrophages, dendritic cells (DCs), neutrophils, M cells and epithelial cells. The ability of Salmonella to invade and survive within a host cell is dependent on two Type III Secretion Systems (T3SS), the multiprotein complexes with a needle-like structure present on the bacteria cell wall. Proteins involved in the assembly of the two major T3SSs of Salmonella are encoded by SPI1 and SPI2.

Salmonella Used as A Tumor Vaccine Vector

The vast majority of tumors express proteins or other antigens that are absent (or present only in very low quantities) in healthy adult tissues. These tumor-associated antigens (TAAs) are potentially immunogenic and tumor development is usually accompanied by specific, although often ineffective, anti-TAA immune response. TAA vaccines used for cancer therapy often fail, probably due to inadequate antigen presentation and insufficient activation of innate immunity. The application of Salmonella as a vector for TAAs should result in overcoming both impediments. The first attempts to deliver TAA via Salmonella were undertaken in late 1990s. From that time numerous studies utilizing natural (mPSCA, mAFP, survivin, endoglin) or artificial (β-galactosidase) tumor antigens have proved that placing a TAA-coding transgene under strong cytomegalovirus promoter in a plasmid carried by Salmonella allows for TAA expression in the cytoplasm of infected cells or dendritic cells which engulfed the infected, apoptotic cells; TAA expression elicits efficient cell-mediated or both cell-mediated and humoral immune responses.

VNP20009, an attenuated mutant of S. Typhimurium, shows significant native toxicity against murine tumors and was studied in a first-in-man phase I clinical trial for toxicity and anticancer activity. While proved to be safe in cancer patients, insufficient tumor colonization of VNP20009 was identified as a major limitation for further clinical development. Antibody-fragment-based targeting of cancer cells is one of the few approaches proposed to overcome this drawback.

Creative Biolabs is a leader in the field of vaccine development and has focused on the cancer vaccines for years. We have experienced experts and advanced platforms that are able to provide excellent services. If you are interested in our services, please contact us for more details.

Reference

1. Chorobik P. (2013). “Salmonella and cancer: from pathogens to therapeutics.” Acta Biochim Pol 60(3), 285-297.

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