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

Marisa Halpern, Muayad A. Zahalka, Leonid Traub, Chaya Moroz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)487-494
Number of pages8
JournalNeoplasia
Volume9
Issue number6
DOIs
StatePublished - Jun 2007
Externally publishedYes

Keywords

  • Antibody
  • Breast cancer
  • Gene
  • Immunomodulator
  • Immunotherapy

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