Cancer Immunotherapy: Priming the Host Immune Response with Live Attenuated Salmonella enterica

Abstract

In recent years, cancer immunotherapy has undergone great advances because of our understanding of the immune response and the mechanisms through which tumor cells evade it. A century after the first immunotherapy attempt based on bacterial products described by William Coley, the use of live attenuated bacterial vectors has become a promising alternative in the fight against cancer. This review describes the role of live attenuated Salmonella enterica as an oncolytic and immunotherapeutic agent, due to its high affinity for tumor tissue and its ability to activate innate and adaptive antitumor immune response. Furthermore, its potential use as delivery system of tumor antigens and immunomodulatory molecules that induce tumor regression is also reviewed.

Inhibition of acute leukemia with attenuated Salmonella typhimurium strain VNP20009

“…However, using natural bacteria to fight leukemia runs the risk of sepsis. In this study, we have chosen a previously engineered and well-characterized attenuated Salmonella Salmonella can also sensitize the host immune system [10], which serves as part of the mechanisms contributing to the efficacy of VNP20009 in treating hematologic malignancies. We found that VNP20009 treatment led to significantly elevated blood levels of proinflammatory cytokines (IFN-γ, TNF-α) and chemokines (CXCL-10 ,CCL-2) in acute leukemia mice, which in turn could recruit a variety of immune cells to participate in the immune response and enhance anti-tumor immunity [5].…”

“…The first bacterial product for cancer immunotherapy was developed by William Coley more than a century ago [7,8]. The past few decades have witnessed the development of bacterial anti-tumor therapy, including the utilization of various bacteria, such as Salmonella, Clostridium and Escherichia coli [9,10]. Among all the anti-tumor bacterial species, Salmonella has been the most studied.…”

“…Among all the anti-tumor bacterial species, Salmonella has been the most studied. In addition to its excellent tumor targeting and colonization ability [11], Salmonella can also activate both the innate and adaptive immune responses against tumors, which has a natural selection advantage in the anti-tumor bacterial therapy [10].…”

“…Previous research using genetic engineering created a Salmonella strain, VNP20009, with a null mutation in msbB gene [12], which leads to greatly reduced production of endotoxin. Such attenuated Salmonella strain has been shown to possess specific targeting and anti-tumor effects to a broad range of solid tumors in mice or spontaneous canine tumors, including melanoma, lung, colon, breast, renal, hepatic tumors [9,10,[13][14][15][16]. Importantly, its tolerance and safety have been proven in patients in a phase I clinical trial [17,18].…”

Nontyphoidal Salmonella : a potential anticancer agent

“…A number of recent reviews have illustrated this role of Salmonella quite elaborately (Wang et al . ; Hernandez‐Luna and Luria‐Perez ; Lawrenz ). It has been hypothesised that the release of various pro‐inflammatory factors of bacterial pathogen‐associated molecular patterns triggers the antitumour activity of S .…”