Targeted delivery of vitamin D analog inhibits Her-2-positive breast cancer cells

A novel vitamin D analog (D5) immunoconjugated to Her-2 antibody targets Her-2-positive breast cancer cells implanted in mice and inhibits tumor growth, according to a report in the March 1st International Journal of Cancer.

“Vitamins and other natural products known to have differentiating and growth inhibitory effects on cancer cells could be used for chemoprevention and therapy of various cancer types,” Dr. Rajeshwari R. Mehta from University of Illinois at Chicago, Chicago, Illinois told Reuters Health. “Targeted delivery of micronutrients will be safe and nontoxic.” Dr. Mehta and colleagues previously showed that D5 had potent cell-differentiating and antiproliferative actions in breast cancer cells in vitro. Here they examined the possible therapeutic potential of targeted delivery of D5 to Her-2-overexpressing breast cancer cells implanted in athymic mice. The D5-Her-2 immunoconjugate induced cell differentiation in the breast cancer cells, the authors report, as evidenced by increased accumulation of intracellular lipid droplets and casein granules. Besides inhibiting in vitro proliferation of BT-474 breast carcinoma cells in vitro, the immunoconjugate significantly reduced mean tumor volumes in female athymic mice transplanted with BT-474 cells, the report indicates. Tumor volumes were similar to those seen in mice that received dietary D5 supplement and smaller than those seen in mice treated with Her-2 antibody alone. Unconjugated D5 administered intraperitoneally did not reduce tumor volumes compared with intraperitoneal injection of solvent, the researchers note. “We are currently testing whether Herceptin (a humanized Her-2 antibody) immunoconjugated to D5 is more effective than either agent given alone,” Dr. Mehta said. “Once we find promising results in experimental animals, the next step will be to study its toxicity.” “The approach to tag vitamin D analog to antibody could be used for any cancer,” the researcher noted. “The Her-2 antibody immunoconjugate approach described in the paper will be more appropriate for Her-2 receptor over-expressing tumors such as breast and some prostate cancers.” “Immunoconjugate therapy could be used to reduce the drug associated toxicity,” Dr. Mehta added. “We can use reduced dose and still could get optimum effect without compromising safety.” (Source: Int J Cancer 2004;108:922-929: Reuters Health: Will Boggs, MD: March 2004: Oncolink)