Bacteria and genetically modified bacteria as cancer therapeutics: Current advances and challenges. (January 2017)

• Record Type: Journal Article
• Authors: Nallar, Shreeram C.; Xu, De-Qi; Kalvakolanu, Dhan V.
• Is Part Of: Cytokine. Volume 89(2017)
• Page Start: 160
• Page End: 172
• Publication Date: 2017-01
• Subjects: Cancer -- Bio-therapy -- Bacterial vectors -- Tumor suppression -- Immune response; BC breast cancer -- CC cervical cancer -- CMV cytomegalovirus -- CRC colorectal cancer -- HCC hepatocellular cancer -- Hly hemolysin, an exotoxin produced by bacteria. -- HSC hematopoietic stem cells -- LC lung cancer -- LPS lipopolysaccharide -- PC prostate cancer -- PSA prostate-specific antigen -- RCC renal cell cancer -- SCC squamous cell cancer -- SPI Salmonella pathogenicity islands -- DLT dose-limiting toxicity – a single minimal dose of a therapeutic agent that results in unacceptable side effects or toxicity in a cohort -- MTD maximum tolerated dose – a single maximal dose of a therapeutic agent that produces the desired response(s) with acceptable side effects or toxicity in a general population. This value is less than DLT -- Exotoxins a family of bacterial proteins secreted or injected using type-I/II secretory apparatus targeting specific host components. Toxins that target host cytosolic proteins include Cholera, Diphtheria, Pertussis and Shiga toxins while another group that creates pores on host cell membrane includes cholesterol-dependent cytolysins and RTX toxins -- Epitope spread a phenomenon where multiple antigen-specific immune responses are triggered that are unrelated, in sequence or structure, to the primary immunogen; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2016.01.002
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: Facultative anaerobic bacteria grow in hypoxic areas of tumors and suppress growth. Bacteria can present tumor-associated peptides to the immune system. Bacterially-delivered mammalian expression plasmids can suppress tumor growth. Bacterial species that can stay in human blood offer more promise to target tumors. Abstract: Bacteria act as pro- or anti- tumorigenic agents. Whole bacteria or cytotoxic or immunogenic peptides carried by them exert potent anti-tumor effects in the experimental models of cancer. The use of attenuated microorganism(s) e.g., BCG to treat human urinary bladder cancer was found to be superior compared to standard chemotherapy. Although the phase-I clinical trials with Salmonella enterica serovar Typhimurium, has shown limited benefits in human subjects, a recent pre-clinical trial in pet dogs with tumors reported some subjects benefited from this treatment strain. In addition to the attenuated host strains derived by conventional mutagenesis, recombinant DNA technology has been applied to a few microorganisms that have been evaluated in the context of tumor colonization and eradication using mouse models. There is an enormous surge in publications describing bacterial anti-cancer therapies in the past 15 years. Vectors for delivering shRNAs that target oncogenic products, express tumor suppressor genes and immunogenic proteins have been developed. These approaches have showed promising anti-tumor activity in mouse models against various tumors. These can be potential therapeutics for humans in the future. In this review, some conceptual and practical issues on how to improve these agents for human applications are discussed.