Phosphatidylserine (PS) is normally intracellular but becomes exposed on the luminal surface of vascular endothelium in tumors and can also be expressed on tumor cells themselves. Studies have shown that targeting PS with an antibody enhances the antitumor effect of chemotherapy or radiation on several tumors, and induces antitumor immunity in mice. Combination of this anti-vascular and antitumor antibody with an antibody (anti-CD47) that blocks the “don’t eat me” signal CD47 commonly expressed on human tumors may lead to synergistic antitumor activity. Similarly, synergistic antitumor activity might be obtained by combining the PS-targeting antibody with anti-CD54, an antibody that has been demonstrated to have pan antitumor activity in xenograft models and is safe in humans. Our objective is to evaluate combinations of these antibodies in a xenograft model of human cancer. Studying these combinations requires determining the expression of CD47 and CD54 on several cancer cell lines. To this end, MDA-MB-231 (breast), NCI-H157 (lung), Du145 (prostate), PANC-1 and BxPC-3 (pancreatic) were analyzed for surface expression of CD47 and CD54. All five cell lines expressed CD47 (>87% of cells positive). All tested cell lines were also highly CD54 positive (>84% of cells positive) except for MDA-MB-231 (~50% positive). The effects of anti-PS antibody in conjunction with anti-CD47 or anti-CD54 on tumor growth are currently being analyzed in SCID mice bearing BxPC-3 pancreatic tumors.
- Copyright © 2013 by The American Association of Immunologists, Inc.