Engineering probiotics for therapeutic applications: recent examples and translational outlook

Aggarwal, Nikhil; Breedon, Amy M. Ehrenworth; Davis, Christina M.; Hwang, In Sung; Chang, Matthew Wook

doi:10.1016/j.copbio.2020.02.016

Cited by 97 publications

(57 citation statements)

References 61 publications

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“…Other than the lack of financial backing, time, and therapeutic potency, the reason why engineered bacterial-based cancer therapies have not been approved for clinical use is concerns about their impact on patient and environmental safety. This has spurred the US FDA and European Pharmacopoeia Commission (EPC) to establish safety guidelines (Guidance on Live Biotherapeutic Organisms, docket number FDA-2010-D-0500) for the translation and commercialization of engineered bacterial-based therapies [124].…”

Section: Box 3 Addressing Safety Concerns For Clinical Translationmentioning

confidence: 99%

Tweak to Treat: Reprograming Bacteria for Cancer Treatment

et al. 2021

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Recent advancements in cancer biology, microbiology, and bioengineering have spurred the development of engineered live biotherapeutics for targeted cancer therapy. In particular, natural tumor-targeting and probiotic bacteria have been engineered for controlled and sustained delivery of anticancer agents into the tumor microenvironment (TME). Here, we review the latest advancements in the development of engineered bacteria for cancer therapy and additional engineering strategies to potentiate the delivery of therapeutic payloads. We also explore the use of combination therapies comprising both engineered bacteria and conventional anticancer therapies for addressing intratumor heterogeneity. Finally, we discuss prospects for the development and clinical translation of engineered bacteria for cancer prevention and treatment. Using Bacteria as Cancer Treatment AgentsIn the landmark review paper 'The hallmarks of cancer' (see Glossary) and its sequel, Hanahan and Weinberg proposed that all cancers display common hallmarks or features that enable the transformation, growth, and progression of normal tissues into tumors [1,2]. Since then, these hallmarks have served as focus areas for researchers to develop novel therapeutic strategies. Current clinical therapies used to manage and treat most cancers include chemotherapy, immunotherapy, hormonal therapy, radiotherapy, and surgery. The choice of therapy, whether monotherapy or combination therapy, used in a treatment plan, varies widely depending on numerous factors, such as the cancer stage, grade, origin, and location within the human body. However, many current anticancer therapies have certain disadvantages, such as: (i) causing pharmacological adverse effects in normal cells; (ii) lacking the ability to penetrate solid tumor tissues; and (iii) being unable to eradicate all cancer cells in the tumor due to the inadvertent acquisition of drug resistance. Hence, there is a dire need to develop novel therapies that could supplement or serve as substitutes to conventional therapies used to treat cancer. In this regard, the use of bacteria for cancer therapy is a unique therapeutic option for consideration. Although there are 200 years of documented history of patients experiencing tumor regression after experimental bacterial infections, bacterial-based cancer treatments did not see much progress, due to reproducibility issues among patients and the rise of radiation therapy and chemotherapy [3]. To date, attenuated Mycobacterium bovis (Bacillus Calmette-Guerin, BCG) is the only bacterial-based cancer therapy that has been clinically approved by the US Food and Drug Administration (FDA) and has been used as one standard of care for high-risk patients with non-muscle-invasive bladder cancer (NMIBC) [4]. Yet, 30-50% of patients fail BCG treatment and~5% of patients have adverse effects, such as tissue sepsis [5].Recent advances in microbiology and bioengineering have restored interest in the development of bacteria-based cancer therapeutics due to their potential to addr...

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Section: Box 3 Addressing Safety Concerns For Clinical Translationmentioning

confidence: 99%

Tweak to Treat: Reprograming Bacteria for Cancer Treatment

et al. 2021

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“…118 The repertoire of engineered immune cells is also being expanded beyond T-cells to include NK cells 119 and macrophages. 120 In addition to immune cells, engineered bacteria, single species or multi-species consortia, are also being developed for skin, gastrointestinal, and other microbiome-associated diseases, [121][122][123][124] and notably for systemic metabolic diseases, where the most advanced developments are already in human clinical trials for phenylketonuria. 125,126 Closely related are bacteriophages as highly potent and specific antimicrobials 127 ; engineered phages were also developed as modulating agents to enhance the effect of chemotherapy in cancer treatment.…”

Section: Next-generation Biomanufacturingmentioning

confidence: 99%

Future trends in synthetic biology in Asia

et al. 2021

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Synthetic biology research and technology translation has garnered increasing interest from the governments and private investors in Asia, where the technology has great potential in driving a sustainable bio-based economy. This Perspective reviews the latest developments in the key enabling technologies of synthetic biology and its application in bio-manufacturing, medicine, food and agriculture in Asia. Asia-centric strengths in synthetic biology to grow the bio-based economy, such as advances in genome editing and the presence of biofoundries combined with the availability of natural resources and vast markets, are also highlighted. The potential barriers to the sustainable development of the field, including inadequate infrastructure and policies, with suggestions to overcome these by building public-private partnerships, more effective multilateral collaborations and well-developed governance framework, are presented. Finally, the roles of technology, education and regulation in mitigating potential biosecurity risks are examined. Through these discussions, stakeholders from different groups, including academia, industry and government, are expectantly better positioned to contribute towards the establishment of innovation and bioeconomy hubs in Asia.

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“…Different fermented food products like yogurt, pickles, kefir or tea like kombucha are the source for probiotics and optimize microbial flora in humans. Non-dairy probiotics can be used in lactose intolerant subjects [15], and engineered probiotics are also available [16].…”

Section: Probioticsmentioning

confidence: 99%

Microbial Therapeutics in Neurocognitive and Psychiatric Disorders

Alagiakrishnan

Halverson

2021

J Clin Med Res

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Microbial therapeutics, which include gut biotics and fecal transplantation, are interventions designed to improve the gut microbiome. Gut biotics can be considered as the administration of direct microbial populations. The delivery of this can be done through live microbial flora, certain food like fiber, microbial products (metabolites and elements) obtained through the fermentation of food products, or as genetically engineered substances, that may have therapeutic benefit on different health disorders. Dietary intervention and pharmacological supplements with gut biotics aim at correcting disruption of the gut microbiota by repopulating with beneficial microorganism leading to decrease in gut permeability, inflammation, and alteration in metabolic activities, through a variety of mechanisms of action. Our understanding of the pharmacokinetics of microbial therapeutics has improved with in vitro models, sampling techniques in the gut, and tools for the reliable identification of gut biotics. Evidence from human studies points out that prebiotics, probiotics and synbiotics have the potential for treating and preventing mental health disorders, whereas with paraprobiotics, proteobiotics and postbiotics, the research is limited at this point. Some animal studies point out that gut biotics can be used with conventional treatments for a synergistic effect on mental health disorders. If future research shows that there is a possibility of synergistic effect of psychotropic medications with gut biotics, then a gut biotic or nutritional prescription can be given along with psychotropics. Even though the overall safety of gut biotics seems to be good, caution is needed to watch for any known and unknown side effects as well as the need for risk benefit analysis with certain vulnerable populations. Future research is needed before wide spread use of natural and genetically engineered gut biotics. Regulatory framework for gut biotics needs to be optimized. Holistic understanding of gut dysbiosis, along with life style factors, by health care providers is necessary for the better management of these conditions.In conclusion, microbial therapeutics are a new psychotherapeutic approach which offer some hope in certain conditions like dementia and depression. Future of microbial therapeutics will be driven by welldone randomized controlled trials and longitudinal research, as well as by replication studies in human subjects.

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Engineering probiotics for therapeutic applications: recent examples and translational outlook

Cited by 97 publications

References 61 publications

Tweak to Treat: Reprograming Bacteria for Cancer Treatment

Tweak to Treat: Reprograming Bacteria for Cancer Treatment

Future trends in synthetic biology in Asia

Microbial Therapeutics in Neurocognitive and Psychiatric Disorders

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