MedWire News: The anti-tumor effects of radiation therapy (RT) could be enhanced using the antiphosphatidylserine antibody 2aG4 to target phosphatidylserine on the luminal surface of tumor blood vessels, thereby making the vessels more vulnerable to cell-mediated cytotoxicity, indicate preliminary study results in mice.

The researchers conducted the study to find out whether RT could increase the exposure of phosphatidylserine on tumor vasculature and so enhance the effects of 2aG4.

Philip Thorpe, from the University of Texas Southwestern Medical Center at Dallas, USA, and colleagues studied the effects of RT plus 2aG4 on mice with radiation-resistant A549 human lung tumors. One group of mice was treated with RT plus 2aG4, while another received 2aG4 alone. A third group of untreated mice acted as controls.

Immunofluorescence staining was used to determine radiation-induced phosphatidylserine exposure on endothelial cells and A549 tumor cells, while histology and antibody-dependent cell-mediated cytotoxicity experiments revealed the mechanism behind improved tumor response.

The results, published in the journal Clinical Cancer Research, show that focal irradiation of the tumor xenografts increased the proportion of tumor vessels with exposed phosphatidylserine, from 4% to 26%. In comparison with 2aG4 alone or no treatment, treating the mice with 2aG4 plus focal RT reduced tumor growth by approximately 80%, a significant difference.

Combination therapy also reduced blood vessel density and enhanced monocyte infiltration into the tumor mass, compared with in other groups, while 2aG4 enhanced the ability of macrophages to kill cultured endothelial cells with exposed phosphatidylserine.

The team concludes: "The present study suggests that clinical evaluation of [2aG4] in combination with RT should be considered for lung cancer patients and patients with other cancers commonly treated with RT."

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