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Review
. 2022 Aug 30;14(17):4224.
doi: 10.3390/cancers14174224.

Recombinant Attenuated Salmonella enterica as a Delivery System of Heterologous Molecules in Cancer Therapy

Elayne Irene Becerra-Báez  1   2 , Sergio Enrique Meza-Toledo  2 , Paola Muñoz-López  1   3   1 , Luis Fernando Flores-Martínez  1   3   1 , Karla Fraga-Pérez  1 , Kevin Jorge Magaño-Bocanegra  1   4 , Uriel Juárez-Hernández  1   4 , Armando Alfredo Mateos-Chávez  1 , Rosendo Luria-Pérez  1
Affiliations
Review

Recombinant Attenuated Salmonella enterica as a Delivery System of Heterologous Molecules in Cancer Therapy

Elayne Irene Becerra-Báez et al. Cancers (Basel). .

Abstract

Over a century ago, bacterial extracts were found to be useful in cancer therapy, but this treatment modality was obviated for decades. Currently, in spite of the development and advances in chemotherapies and radiotherapy, failure of these conventional treatments still represents a major issue in the complete eradication of tumor cells and has led to renewed approaches with bacteria-based tumor therapy as an alternative treatment. In this context, live-attenuated bacteria, particularly Salmonella enterica, have demonstrated tumor selectivity, intrinsic oncolytic activity, and the ability to induce innate or specific antitumor immune responses. Moreover, Salmonella enterica also has strong potential as a delivery system of tumor-associated antigens, cytotoxic molecules, immunomodulatory molecules, pro-apoptotic proteins, and nucleic acids into eukaryotic cells, in a process known as bactofection and antitumor nanoparticles. In this review, we present the state of the art of current preclinical and clinical research on the use of Salmonella enterica as a potential therapeutic ally in the war against cancer.

Keywords: Salmonella enterica; cancer therapy; immunotherapy.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflict of interest.

Figures

Figure 1
Figure 1
Tumor selectivity and inherent antitumor activity of Salmonella enterica. After Salmonella enterica enters the host through the mucosas or intravenously, it can specifically target tumor tissue due to hypoxia, acidity, necrosis, suppressed immune response, and the presence of chemoattractants of the bacterium in the tumor microenvironment. Subsequently, Salmonella enterica, activates inherent antitumor mechanisms, including its oncolytic activity per se, and the induction of the innate and adaptive immune responses.
Figure 2
Figure 2
Salmonella enterica as a delivery system of heterologous molecules in cancer therapy. Salmonella enterica’s tropism for the tumor microenvironment and antigen-presenting cells (APC), as well as its ability to become a molecule factory within the tumor microenvironment, has allowed its use as a delivery system of heterologous molecules with antitumor properties such as: tumor-associated antigens or tumor-specific antigens, cytotoxic molecules, immunomodulating molecules, inducers of apoptosis, nucleic acids, and nanomolecules.
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