Bacteriophage therapy
binding and attachment), and the first report can be dated back to 1958. 52 The ability of phages to effectively interact with cancer cells and deliver therapeutic payloads, the increasing demand in therapeutic approach for cancer treatment, along with an increasingly improving understanding of phage biology and the technology of genetic engineering, have brought phages into a new clinical area under the spotlight. Specific therapeutic approaches involving phages to treating cancers include phage-mediated gene therapy, phage-mediated chemotherapeutic drug delivery, and phage-based cancer immunotherapy (stimulation of immune response to prevent or treat cancers). 53 Cancer gene therapy refers to the delivery of a functional therapeutic gene to target cancer cells, thereby resulting in the inhibition of certain macromolecular expression, over-expression of a specific protein, direct induction of cell death, or inactivation/replacement of a defective gene (e.g., oncogene) to help restore normal genes and normalize cell functions. 54
P
Figure 4
Ontology of Phage Applications for Cancer Biology and Treatment
Note. This figure illustrates some of the key areas in which phage therapy may be applied for cancer treatment. This figure is covered by the Creative Commons (CC) Attribution 4.0 International License. Reprinted from Clinics in Oncology, Bacteriophages in Cancer Biology and Therapies, Swapnil Ganesh Sanmukh & Sérgio Luis Felisbino (2017).
Przystal et al. reported a series of experiments in 2019 examining the efficacy of genetically modified temozolomide-activated M13 phage in the phage-mediated gene therapy for glioblastoma tumours. In the controlled experiments, glioblastoma tissues obtained from deceased human adults and children were transplanted into the brains of mice. The genetically modified M13 phages used were capable of specifically targeting glioblastoma tumour cells and delivering an anti-cancer gene payload. M13 phages concentrated only at the site of glioblastomas, leaving the surrounding healthy cells unaffected. Together with an anti-cancer drug named Temozolomide (TMZ), the process of the phage-mediated gene therapy was amplified, and the efficacy was improved compared to gene therapy alone. At the cellular level, M13 phages were engineered to be multifunctional and are able to target three types of malignant cells within glioblastomas: glioblastoma tumour cells, undifferentiated stem cells, and cancer blood vessel cells. A satisfactorily high survival rate among the mice receiving phage-TMZ therapy was observed (in some cases, more than 84 days after the tumour transplantation). 55 This type of cancer gene therapy is currently in the transition stage between laboratory testing and RCTs on humans. In an in vitro experiment conducted by Bar et al. (2008), genetically-modified and chemically manipulated filamentous bacteriophages were used to deliver chemotherapeutic agents via phage display. A large payload of a cytotoxic drug was chemically conjugated to specific genetically- engineered sites on the phage capsids, to which specific antibodies that target and bind with the cancer
52 Dąbrowska et al. 2004. 53 Hess & Jewell 2019. 54 Pranjol & Hajitou 2015. 55 O’Hare 2019.
264
Made with FlippingBook interactive PDF creator