Tumour-targeting bacteria engineered to fight cancer

Abstract

Recent advances in targeted therapy and immunotherapy have once again raised the hope that a cure might be within reach for many cancer types. Yet, the majority of cancers are either insensitive to the therapies to begin with or develop resistance later on. Therapy with live tumor-targeting bacteria provides a unique option to meet these challenges. Compared to most other therapeutics, the effectiveness of tumor-targeting bacteria is not directly affected by the genetic makeup of a tumor. Bacteria initiate their direct antitumor effects from deep within the tumor, followed by innate and adaptive antitumor immune responses. As microscopic “robotic factories”, bacterial vectors can be reprogrammed following simple genetic rules or sophisticated synthetic bioengineering principles to produce and deliver anticancer agents based on clinical needs. Therapeutic approaches using live tumor-targeting bacteria can either be applied as a monotherapy or complement other anticancer therapies to achieve better clinical outcomes. In this Review, we summarize the potential benefits and challenges of this approach. We discuss how live bacteria selectively induce tumor regression and provide examples to illustrate different ways to engineer bacteria for improved safety and efficacy. Finally, we share our experience and insights on oncology clinical trials with tumor-targeting bacteria, including a discussion on regulatory issues.

Investigating the physical effects in bacterial therapies for avascular tumors

“…cytotoxic agents, prodrug-converting enzymes, etc. (Torres et al, 2018; Zhou et al, 2018; Kramer et al, 2018). Such treatment modalities could be incorporated by extending the model, to provide a more accurate description of the therapeutic action.…”

“…by realising toxins and therapeutic agents, or stimulating an immune response). (Forbes, 2010; Osswald et al, 2015; Torres et al, 2018; Zhou et al, 2018).…”

“…In the last few years the use of live bacteria for cancer treatment has gained new interest, and several bacterial strains have been tested in animal models and even advanced to clinical trials (Torres et al, 2018). Nevertheless, clinical development of such therapies is still facing significant issues due to infection-associated toxicities and incomplete knowledge of infection dynamics (Kramer et al, 2018; Zhou et al, 2018).…”

Self‐Mineralized Photothermal Bacteria Hybridizing with Mitochondria‐Targeted Metal–Organic Frameworks for Augmenting Photothermal Tumor Therapy

“…Also, bacteria as a kind of living organism, their metabolites can directly exert significant tumor suppression effect 4,6. Bacteria can also be genetically manipulated to produce targeting anticancer drugs to meet clinical needs 3,7. Additionally, bacteria are convenient to be chemically modified because of abundant chemical groups presenting on their surface 1,8.…”

“…[4,6] Bacteria can also be genetically manipulated to produce targeting anticancer drugs to meet clinical needs. [3,7] Additionally, bacteria are convenient to be chemically modified because of abundant chemical groups presenting on their surface. [1,8] Given these advantages, versatile bacteria-based tumor therapeutic as mitochondria-targeted drug carrier for mitochondria interference.…”