Phage and Cancer
Introduction
Phage have been receiving more attention for their ability to fight antibiotic-resistant bacterial infections, but they have also been shown to have anticancer activity. The anticancer activity has been attributed to the their ability to activate the immune response as well as their ability to serve as a platform for drugs. [1]
History
The potential for phage in cancer treatment was first demonstrated in the 1940s when Bloch noted an excess phage development in cancer cells resulting in the retardation of tumor growth. [1] Later studies confirmed that several phage bind to cancer cells. For example, Krystyna Dabrowska found T4 phage to transiently bind to melanoma cells.[2] When mutants were selected for, strong interactions between the phage and cancer cells were observed. Such mutants were administered to rats with induced melanoma, and although no regression of cancer occurred, some cancer cell growth was inhibited.
Immune System Response
Although phage cannot cause mammalian cell lysis, they have been known to induce an immune respomse by stimulating the immune system to make antibodies against the phage. This has been a source of problems in the application of phage meant to target bacterial infections, as it minimizes the chances of the phage reaching the bacteria. However, this fact can be exploited in cancer fighting mechanisms. For example, purified T4 phage were observed to increase the function of dendritic cells in inhibiting tumor growth. Dendritic cells present tumor associated antigens to T cells, thereby mounting an immune response against cancer. A recent study found that mouse colon carcinoma growth was greatly inhibited when T4 was allowed to interact with dendritic cells.[3]
Besides activating dendritic cells, phage have also been shown to activate lymphocytes and macrophages, particularly in melanoma and colon cancers [4] Bacteriophage were shown to induce the tumor killing properties of macrophages and eliminate the macrophages that supress cancer fighting T cells. [4]
Cancer and Phage display
Phage display has also shown to be useful in cancer treatment. This technique involves the insertion of a gene coding a particular protein on a phage, causing it to display this desired protein. In this case, the phage itself does not engage in anticancer activity, but rather presents anticancer peptides. Phage are the ideal delivery system as they are easily manipulated and engineered.[5]
Phage Therapy for Cancer Patients
Cancer patients are often vulnerable to bacterial infections as the result of a weakened immune system. Phage can be used to target antibiotic resistant infections, without wrecking havoc on the rest of the body. A recent study used bacteriophage to treat infections in 20 cancer patients that did not respond to antibiotics. The phage successfully eliminated the infection in every patient without adverse side effects. Furthermore, the phage seemed to enhance immune system function in some of the patients. [6] In addition, an 1989 study found phage to be effective in over 80 percent of cancer patients with infections associated with surgical wounds. [7]
References
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- ↑ 1.0 1.1 Budynek, P et al. (2010) Bacteriophages and cancer. Arch. Microbiol. 192 315-20 PubMed
- ↑ Dabrowska, K et al. (2009) The effect of bacteriophages T4 and HAP1 on in vitro melanoma migration. BMC Microbiol. 9 13 PubMed
- ↑ Pajtasz-Piasecka, E et al. (2008) Bacteriophages support anti-tumor response initiated by DC-based vaccine against murine transplantable colon carcinoma. Immunol. Lett. 116 24-32 PubMed
- ↑ 4.0 4.1 Eriksson, F et al. (2009) Tumor-specific bacteriophages induce tumor destruction through activation of tumor-associated macrophages. J. Immunol. 182 3105-11 PubMed
- ↑ Jin, SE et al. (2014) Targeted delivery system of nanobiomaterials in anticancer therapy: from cells to clinics. Biomed Res Int 2014 814208 PubMed
- ↑ Górski, A et al. (2009) Bacteriophage therapy for the treatment of infections. Curr Opin Investig Drugs 10 766-74 PubMed
- ↑ Mathur, MD et al. (2003) Bacteriophage therapy: an alternative to conventional antibiotics. J Assoc Physicians India 51 593-6 PubMed
