Recent Advances and Mechanisms of Phage-Based Therapies in Cancer Treatment

Abstract

The increasing interest in bacteriophage technology has prompted its novel applications to treat different medical conditions, most interestingly cancer. Due to their high specificity, manipulability, nontoxicity, and nanosize nature, phages are promising carriers in targeted therapy and cancer immunotherapy. This approach is particularly timely, as current challenges in cancer research include damage to healthy cells, inefficiency in targeting, obstruction by biological barriers, and drug resistance. Some cancers are being kept at the forefront of phage research, such as colorectal cancer and HCC, while others like lymphoma, cervical cancer, and myeloma have not been retouched in a decade. Common mechanisms are immunogenic antigen display on phage coats and the use of phage as transporters to carry drugs, genes, and other molecules. To date, popular phage treatments being tested are gene therapy and phage-based vaccines using M13 and λ phage, with some vaccines having advanced to human clinical trials. The results from most of these studies have been promising, but limitations in phage-based therapies such as reticuloendothelial system clearance or diffusion inefficiency must be addressed. Before phage-based therapies for cancer can be successfully used in oncology practice, more in-depth research and support from local governments are required.

Keywords: cancer therapy; gene therapy; immunity; peptide display; phage.

Figure 1

Mechanisms of phage-based cancer therapies (using filamentous phage as an example). (A) Cancer cell antigens can be displayed on phage surface using peptide display technique. These antigens can trigger an immune response, encourage production of anti-cancer antibodies, or activate cytotoxic T cells against cancer cells. (B) Phages can be used as transporters to deliver photosensitizers, cytokines, or transgenes to cancer cells. APC, antigen presenting cell; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand; pIII, M13 pIII coat protein; pVIII, M13 pVIII coat protein.