Bacteriophages have emerged as an innovative solution for the delivery of genes and drugs in cancer therapy. Responsible for approximately 10 million deaths every year, cancer represents a key area of research and healthcare in which novel biotechnologies (such as bacteriophages) can make a considerable impact. This blog will therefore examine the application of bacteriophages in cancer therapy, highlighting the ongoing research and where the field is heading in the future.
Bacteriophages and Cancer Therapy
Bacteriophages are a highly diverse group of bacterial viruses, capable of infecting almost all types of existing bacteria. Bacteriophages have natural antibacterial activity – they inject their genetic material into the host cell, which results in cell lysis or the disruption of metabolism and bacterial cell death. In recent years, bacteriophages have seen a wide range of biological applications, with increasing studies confirming the efficacy and safety of phage-based vectors as delivery tools in cancer therapy.
Within cancer therapy, bacteriophages fall into the category of personalised medicine. The individual tailoring of personalised medicine means that the adaptive and heterogeneous behaviour of tumours can be targeted, an advantage over traditional cancer therapies. Much research is ongoing, exploring the use of bacteriophages in the delivery of high-payload therapeutics to cancer cells, DNA and RNA delivery in gene therapy, and immuno-oncology with phage vaccine carriers.
Phages Targeting Cancer Cells
Bacteriophages have been engineered to specifically target cancer cells by displaying foreign proteins or peptides, a well-established molecular technique known as phage display. By displaying known tumour-targeting peptides, or peptides that bind to cancer cell-specific markers and receptors, precision-engineered bacteriophages can specifically target cancer cells and avoid unwanted side effects against healthy tissue.
Aside from the precision medicine aspect, targeting cancer with bacteriophages has several distinct advantages over traditional anticancer therapies. Firstly, phages can be conjugated to any drug or carrier with a simple and cheap chemistry. Phages have been engineered to efficiently carry diverse payloads such as fluorescent dyes, photosensitizers, small nanoparticles, proteins, chemotherapeutic drugs, small interfering RNA, CRISPR-Cas systems, and large mammalian gene expression cassettes.
Gene therapy is an experimental approach to treating diseases based on the transfer of genetic material into disease cells. Within cancer, there are increasing studies confirming the efficacy and safety of phage-based vectors as systemic delivery vehicles for therapeutic genes. Engineered bacteriophages have demonstrated much greater transgene delivery and expression in cancer cells compared to non-viral gene transfer methods, whilst also producing fewer side effects than eukaryotic virus-based vectors.
Bacteriophages can also be exploited to display specific peptides that aid in crossing biological barriers, such as the blood-brain barrier (BBB). This means that phages have been highlighted as a powerful therapy in Glioma, the most common cerebral cancer with high morbidity and mortality. On top of being able to cross the BBB, phage-based drugs can also cross the blood-brain tumour barrier (BBTB), a significant hurdle in which most antitumor drugs fail.
Phages Enhancing Immune Response
Phage display and engineered bacteriophages have also been harnessed in cancer immunotherapy, and phage vaccines have been developed to enhance immune response. When a phage has been engineered to display a cancer-specific antigen on its surface, it can trigger an enhanced immune response against the cancer cells it is targeting. This response can be immunogenic, involving the production of antibodies, or immunomodulatory, affecting different populations of immune cells involved in innate and adaptive immunity.
Bacteriophages and phage display have been highlighted as a promising approach towards vaccine development. Phage display vaccines express multiple copies of an antigen on the surface of immunogenic phage particles, thereby eliciting a powerful and effective immune response. Within cancer, phage-based vaccines have shown advantages over standard vaccines, with increased T-cell activation and the stimulation of an optimal immune response. Bacteriophage DNA vaccines have been highlighted as being particularly useful in cancer therapy, as the phage genome is suitable for the insertion of large DNA sequences and the bacteriophage is only able to replicate in the targeted tumour cells.
Bacteriophages in Human, Harvest, and Animal Health
Aside from cancer therapy, bacteriophages have been identified as potential solutions across many key areas in human, harvest, and animal health. A significant threat to human health is the rapid increase of multi-drug-resistant bacteria, with bacteriophages presented as a potentially revolutionary solution to antibiotic resistance.
There has been considerable interest in the use of phages as biocontrol agents for foodborne pathogens in animals used for food production and in food products themselves. The most commonly reported source of food-borne infections is poultry meat, and commercial bacteriophages have shown effective elimination of infectious bacteria in chicken breast fillets.
The use of bacteriophages has also been explored in harvest health, where losses in crop yields need to be addressed in order to meet increasing global food demands. Low crop yields can be caused by bacterial crop disease, which is also increasing due to bacterial resistance. Bacteriophages have been proposed as a means of addressing bacterial crop disease, to increase yields whilst also being more environmentally friendly.
Cancer therapy represents a key area in which bacteriophages can make a considerable impact. From targeting cancer cells and personalised medicine to enhancing immune response and phage vaccines, bacteriophages have the potential to revolutionise the way cancer is treated and save millions of lives every year. The current research is very promising but continued research and clinical trials into bacteriophages and their application within cancer therapy is essential. In turn, this would open up the clinical use of bacteriophages within cancer therapy including the use of cancer-targeting drugs and vaccines.