Therapeutic bacteria to combat cancer; current advances, challenges, and opportunities

Abstract

Successful treatment of cancer remains a challenge, due to the unique pathophysiology of solid tumors, and the predictable emergence of resistance. Traditional methods for cancer therapy including radiotherapy, chemotherapy, and immunotherapy all have their own limitations. A novel approach is bacteriotherapy, either used alone, or in combination with conventional methods, has shown a positive effect on regression of tumors and inhibition of metastasis. Bacteria‐assisted tumor‐targeted therapy used as therapeutic/gene/drug delivery vehicles has great promise in the treatment of tumors. The use of bacteria only, or in combination with conventional methods was found to be effective in some experimental models of cancer (tumor regression and increased survival rate). In this article, we reviewed the major advantages, challenges, and prospective directions for combinations of bacteria with conventional methods for tumor therapy.

From cellular microbiology to bacteria‐based next generations of cancer immunotherapies

“…Bacteria–host interactions also trigger in vivo potent host immune responses. These bacterial‐driven immune responses have been exploited from long in antitumour therapies (Kramer, Masner, Ferreira, & Hoffman, ; Sedighi et al, ) but less is known about the exact mechanisms that finally triggered antitumour activity. Besides classical forms of tumour treatments such as radiation and chemical therapy, an emerging field, revolutionising oncology, regards the use immunotherapies, allowing the treatment of tumours with otherwise very bad prognosis (Chen & Mellman, ).…”

“…Similarly, it has been shown that some bacteria have a preference to grow in the hypoxic/inmunosupressive ambient of solid tumours (like Salmonella spp, L. monocytogenes or Clostridium spp) and this ability could be combined with cytotoxic toxins to kill target cells (Sedighi et al, ). There is an increasing effort to engineer safe bacteria to improve the selective elimination of the tumour, which in addition could increase the ‘immunological death’ of tumour cells, liberating danger signals, activating the immune system, and therefore enhancing the antitumor effect of the bacteria‐based antitumor treatment (Galluzzi, Buqué, Kepp, Zitvogel, & Kroemer, ).…”

“…Is it also possible that bacteria‐induced tumour death increases the tumour‐antigen spread, contributing also to tumour detection and elimination by the immune system (Gulley et al, ). Similarly, the ability of bacteria to induce potent immune responses could be used in novel cancer immunotherapies using modified bacteria expressing tumour antigens as antitumour vaccines (Flickinger et al, ; Sedighi et al, ).…”

Bioinspired Engineering of a Bacterium‐Like Metal–Organic Framework for Cancer Immunotherapy

“…[1,4,7] Moreover, bacterial injections can induce necrotic cells to generate heat shock proteins, such as HSP70, resulting in the maturation of antigen presenting cells (APCs), which participate extensively in antitumor activities. [8,9] The antitumor response of bacteria is also likely to be associated with the adjuvant effect of their microbial-associated molecular pattern molecules, including fimbriae and lipopolysaccharide. [9,10] Although BMTT is regarded as effective, the use of bacteria in antitumor treatment has never become a routine clinical practice because of the risk that bacterial toxins cause infections.…”

Development of Dual-Scale Fluorescence Endoscopy for In Vivo Bacteria Imaging in an Orthotopic Mouse Colon Tumor Model

“…In addition, bacterial infection activates host immunity and promotes a therapeutic effect [12,13]. Salmonella is bacteria with multiple anti-tumor functions, including tumor targeting, intratumoral penetration, direct tumor killing, anti-angiogenic, and immune activation [14][15][16][17]. Phase I clinical trials using salmonella have been allowed by the United State Food and Drug Administration (FDA) for advanced cancer patients [18][19][20].…”