Hacking the Immune Response to Solid Tumors: Harnessing the Anti-Cancer Capacities of Oncolytic Bacteria

Oncolytic bacteria are a classification of bacteria with a natural ability to specifically target solid tumors and, in the process, stimulate a potent immune response. Currently, these include species of Klebsiella, Listeria, Mycobacteria, Streptococcus/Serratia (Coley's Toxin), Proteus, Salmonella, and Clostridium. Advancements in techniques and methodology, including genetic engineering, create opportunities to hijack typical host-pathogen interactions and subsequently harness oncolytic capacities. Engineering, sometimes termed domestication, of oncolytic bacterial species is especially beneficial when solid tumors are inaccessible or metastasize early in development. This review examines reported oncolytic bacteria-host immune interactions and details the known mechanisms of these interactions to the protein level. A synopsis of the presented membrane surface molecules that elicit particularly promising oncolytic capacities is paired with the stimulated localized and systemic immunogenic effects. In addition, oncolytic bacterial progression toward clinical translation through engineering efforts are discussed, with thorough attention given to strains that have accomplished Phase III clinical trial initiation. In addition to therapeutic mitigation after the tumor has formed, some bacterial species, referred to as prophylactic, may even be able to prevent or derail tumor formation through anti-inflammatory capabilities. These promising species and their particularly favorable characteristics are summarized as well. A complete understanding of the bacteria-host interaction will likely be necessary to assess anti-cancer capacities and unlock the full cancer therapeutic potential of oncolytic bacteria.

Automated summary

Oncolytic bacteria are a type of bacteria that can specifically target tumors and stimulate immune responses. Through techniques like genetic engineering, these bacteria can be modified to enhance their ability to kill tumor cells, which is particularly useful for tumors that are difficult to access or have spread at an early stage. This review examines the interactions between oncolytic bacteria and the immune system, and discusses the potential of using these bacteria as cancer therapeutics. The review also discusses the progress of oncolytic bacteria in clinical trials and highlights the characteristics of bacteria that have shown promising results.