Recent advances in bacteria-mediated cancer therapy

Abstract

Cancer is among the leading cause of deaths worldwide. Although conventional therapies have been applied in the fight against the cancer, the poor oxygen, low extracellular pH, and high interstitial fluid pressure of the tumor microenvironment mean that these treatments fail to completely eradicate cancer cells. Recently, bacteria have increasingly been considered to be a promising platform for cancer therapy thanks to their many unique properties, such as specific tumor-targeting ability, high motility, immunogenicity, and their use as gene or drug carriers. Several types of bacteria have already been used for solid and metastatic tumor therapies, with promising results. With the development of synthetic biology, engineered bacteria have been endowed with the controllable expression of therapeutic proteins. Meanwhile, nanomaterials have been widely used to modify bacteria for targeted drug delivery, photothermal therapy, magnetothermal therapy, and photodynamic therapy, while promoting the antitumor efficiency of synergistic cancer therapies. This review will provide a brief introduction to the foundation of bacterial biotherapy. We begin by summarizing the recent advances in the use of many different types of bacteria in multiple targeted tumor therapies. We will then discuss the future prospects of bacteria-mediated cancer therapies.

Arginine-linked HPV-associated E7 displaying bacteria-derived outer membrane vesicles as a potent antigen-specific cancer vaccine

“…Current advanced cancer immunotherapy treatments boost humoral and cellular immunity without the non-specific targets and toxic effects on normal cells as conventional cancer treatment [ 1 , 2 ]. However, despite these advances, the inability to predict treatment efficacy, the need for additional biomarkers, the development of resistance to cancer immunotherapies, and the high treatment costs continue to serve as a limitation in immunotherapeutic treatments [ 3 , 4 ].…”

Salmonella immunotherapy engineered with highly efficient tumor antigen coating establishes antigen-specific CD8+ T cell immunity and increases in antitumor efficacy with type I interferon combination therapy

“…With improvements in genetic engineering techniques, bacteria-based cancer therapies have gained increasing attention as a versatile complement to conventional treatment strategies. 1 , 2 Recent discoveries have shed light on their cancer therapeutic characteristics, including specific targeting hypoxic tumor microenvironment (TME) by anaerobic strains, immunostimulatory action on professional antigen-presenting cells (APCs) and cascade responses, and diverse modifications for improved antitumor activities. 3–7 Among these therapeutic bacterial species, Salmonella (S. typhimurium) is one of the most well-researched and promising candidates, due to its superior tumor targeting and growth suppression abilities.…”

Genetically engineered bacteria: a new frontier in targeted drug delivery

“…20,23 Despite advancements in bacteria-mediated cancer therapy and targeted drug delivery, there are some pivotal challenging issues that need to be considered before their widespread biomedical applications, including potential pathogenicity and toxicity, lack of knowledge on mechanisms and side effects, complex physiological barriers, limited tumor penetration, immune system response, and ethical considerations. [24][25][26][27] Notably, the employment of live bacteria for cancer therapy carries the risk of systemic infections, which can be lifethreatening. This risk can be mitigated by applying attenuated or GEB that are less virulent.…”

“…This risk can be mitigated by applying attenuated or GEB that are less virulent. 26 Though, more elaborative studies are still warranted to focus on crucial aspects such as biological safety and environmental containment/survival of GEB for drug delivery in humans, and their use requires comprehensive clinical evaluations. 6,28 For instance, one approach to ensure safety is the employment of thymineless death as a containment strategy, involving the engineering of bacteria to be dependent on an external supply of thymine that is essential for their survival; without thymine, the GEB cannot replicate and eventually die off.…”