Antibodies to placental immunoregulatory ferritin with transfer of polyclonal lymphocytes arrest MCF-7 human breast cancer growth in a nude mouse model

The recently cloned human gene named "placental immunoregulatory ferritin" (PLIF ) is a pregnancy-related immunomodulator. Recombinant PLIF and its bioactive domain C48 are immune-suppressive and induce pronounced IL-10 production by immune cells. PLIF is expressed in the placenta and breast cancer cells. Blocking PLIF in pregnant mice by anti-C48 antibodies inhibited placental and fetal growth and modulated the cytokine network. It has been revealed that anti-C48 treatment inhibited MCF-7 tumor growth in nude mice. However, this significant effectwas observed only in those transfused with human peripheral blood mononuclear cells. Blocking PLIF in tumor-engrafted human immune cell transfusedmice resulted inmassive infiltration of human CD45⁺ cells (mainly CD8⁺ T cells), both intratumorally and in the tumor periphery, and a significant number of caspase-3⁺ cells. In vitro, anti-C48 treatment of MCF-7 tumor cells cocultured with human lymphocytes induced a significant increase in interferon-γ secretion. We conclude that blocking PLIF inhibits breast cancer growth, possibly by an effect on the cytokine network in immune cells and on breakdown of immunosuppression.