Bacteria−Based Synergistic Therapy in the Backdrop of Synthetic Biology

Abstract

Although the synergistic effect of traditional therapies combined with tumor targeting or immunotherapy can significantly reduce mortality, cancer remains the leading cause of disease related death to date. Limited clinical response rate, drug resistance and off-target effects, to a large extent, impede the ceilings of clinical efficiency. To get out from the dilemmas mentioned, bacterial therapy with a history of more than 150 years regained great concern in recent years. The rise of biological engineering and chemical modification strategies are able to optimize tumor bacterial therapy in highest measure, and meanwhile avoid its inherent drawbacks toward clinical application such as bacteriotoxic effects, weak controllability, and low security. Here, we give an overview of recent studies with regard to bacteria-mediated therapies combined with chemotherapy, radiotherapy, and immunotherapy. And more than that, we review the bacterial detoxification and targeting strategies via biological reprogramming or chemical modification, their applications, and clinical transformation prospects.

Potential role of intratumor bacteria outside the gastrointestinal tract: More than passengers

“…With the development of genetic editing technology, we can attenuate the virulence of bacteria, as well as improve its anti‐cancer efficiency through manual intervention 108 . Researchers have modified Salmonella , Listeria , and Clostridium to boost the tumor‐targeting capabilities of obligate anaerobic bacteria and minimize the systemic toxicity of facultative anaerobic bacteria 109 . Therefore, attenuated, low‐toxic bacteria are increasingly being employed as anti‐cancer medications or therapeutic platforms.…”

“… 108 Researchers have modified Salmonella , Listeria , and Clostridium to boost the tumor‐targeting capabilities of obligate anaerobic bacteria and minimize the systemic toxicity of facultative anaerobic bacteria. 109 Therefore, attenuated, low‐toxic bacteria are increasingly being employed as anti‐cancer medications or therapeutic platforms. In fact, the relationship between intratumor bacteria and bacteria‐based therapies is intimated.…”

Chemical and Synthetic Biology Approaches for Cancer Vaccine Development

“…In 1868, William Coley infected cancer patients with Streptococcus pyogenes species of bacteria. [ 94 ] Surprisingly, some patients witnessed reduced tumor size or complete disappearance of tumors, suggesting that bacterial therapy could be a valuable option for cancer research [ 94 ]. The only licensed example of a live bacteria-based vaccine being used to treat cancer is the Bacillus Calmette-Guérin (BCG) vaccine, which contains an attenuated strain of Mycobacterium bovis , and has been successfully applied to treat superficial bladder cancer [ 95 ].…”

“…Furthermore, a nonpathogenic Escherichia coli strain was bio-engineered with a controllable nanobody (anti-CD47) to effectively activate the infiltration of cytotoxic T lymphocytes [ 100 ]. Bacteria can also be genetically modified to express TAAs, bacterial toxins, and cytokines [ 94 ]. For instance, Salmonella ser.…”