Bacteriophages in Cancer Biology and Treatment
Section
By Salome Shubitidze!
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The use of Bacteriophages for drug delivery
Chemotherapy drugs, while shown to have anti-tumor effects, tend to result in severe toxicity and widespread distribution throughout the body: notably damaging healthy and malignant cells. New research has started to focus on using bacteriophages as an individualized drug-carrying anti-cancer therapy. The therapy would be targeted, based on genetically-modifying and chemically manipulating filamentous bacteriophages. In Bar et al. 2008, the phages were modified to display a host-specificity-conferring ligand, and carry a cytotoxic drug by chemical conjugation
Antibodies anti ErbB2 and anti ERGR were used to direct bacteriophages to cancer cells. ErbB2 is a a well known protein that is found to be over expressed in approximately 20% of invasive breast cancers. ERGR is a receptor protein that is found on the surface of cells that causes some cells to duplicate if an epidermal growth factor binds to it. They both belong to the epidermal growth factor receptor (EGFR) family (19). They are both common proteins that tend to be associated with the growth of cancers. The cell lines used in Bar et al. 2008 were SKBR3 and MDA-MB23 (human breast carcinoma cell lines), A431 (human epidermoid carcinoma), and HEK293 (human kidney). Phages were engineered to be linked to respective antibodies. A whole cell ELISA was performed in order to assess the binding of phage-attached antibodies (see figure 1.) MDA-MB231 cells express a low level of ErbB2 proteins, while SKBR3 express a much higher level of ErbB2 proteins. As shown, one can see that the antibody-complexed phages showed cell-specific binding. The engineered fUSE5-ZZ-chFRP5 phage had higher rates of binding to receptors on SKBR3 and even MDA-MB231 than the control phage fUSE5-ZZ-human IgG. This shows that antibody-attached phages are capable of attaching to their respective receptors.
In order to check if phages could effectively deliver drugs, researchers had to verify that they could enter into host cells. One way this was done was by visualizing phage internalization using confocal microscopy and immunofluorescence staining.
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Changing the Tumor Microenvironment
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Phage Display Methods and Tumor-specific Antibody–receptor Pairs
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Activating the Innate Immune System
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Authored for BIOL 238 Microbiology, taught by Joan Slonczewski, 2018, Kenyon College.
