The bacteriophage T4 preparation (BP T4)* was obtained and purified at the Ludwik Hirszfeld Institute of Immunology and Experimental Therapy in Wrocław. BP T4 purification enabled concentration of the phage suspension and partial removal of most of its contaminants. However, endotoxins (LPS), despite their relatively low molecular weight, were not completely removed and their concentration in the final bacteriophage preparation was less than 10 EU/mL [1].

BP T4 is a biologically active agent exhibiting antitumor effect. As previously shown, BP T4 binds to cancer cells and shows antitumour and antimetastatic effect in murine experimental tumor models [2, 3]. This binding may explain the mechanism of bacteriophage-eukaryotic cell interactions and the observed biological effect. According to our hypothesis, this binding is mediated by the gp24 phage head protein and b3 integrins expressed on mouse tumor cells. Bacteriophage gp24 contains KGD amino-acid motifs, i.e. RGD homologues able to bind b3 integrins' receptors [4].

The aim of this study was to verify the possible effect on experimental lung metastases in mice injected i.v. with B16 melanoma. The effect of BP T4 administration on the effectiveness of known anticancer agents (cyclophosphamide, cisplatine, or 5-fluorouracile) was studied. C57Bl/6 mice were daily injected intraperitoneally with BP T4 in a dose of 10⁹ pfu/mouse for 21 days. We used two control groups, one injected with physiological saline and one with a solution of LPS in a concentration as in BP T4. The bacteriophage T4 preparation was applied together with a single dose of cyclophosphamide, cisplatine, or 5-fluorouracile (in doses of 50, 5, or 100 mg/kg, respectively). The mice were maintained under standard laboratory conditions. They were sacrificed by cervical dislocation 21 days after tumor inoculation and the experimental metastatic lung colonies were counted.
A decrease in the number of metastasis formations was observed in the lungs of the mice treated with cyclophosphamide combined with BP T4 (72% compared with the control, p<0.01). The decrease in lung metastasis loci in the mice treated with BP T4 alone was in the range of 35% to 50% in two independent experiments (p>0.05). These results corresponds with our previous data [2, 3]. The biological effect of LPS used alone was observed whereby the number of metastases was reduced by 18% or 42% (p>0.05). We did not observe any enhanced antimetastatic effect of BP T4 applied together with cisplatine or with 5-fluorouracile, although the antimetastatic effect of these cytostatics was observed (63% and 20%, respectively).These data show that our bacteriophage preparation can influence the antimetastatic activity of cyclophosphamide. We suppose that the modifying effect of the bacteriophage preparation could be related to the drug's mechanism of action. This phenomenon requires further study.

1. Boratyński J. et al., Cellular and Molecular Biology Letters, 2004.

2. Dąbrowska K. et al., Acta Virologica, 2004.

3. Dąbrowska K. et al., Anticancer Research, 2004.

4. Górski A. et al., Medical Immunology, 2003.

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