The novel C24D synthetic polypeptide inhibits binding of placenta immunosuppressive ferritin to human T cells and elicits anti-breast cancer immunity in vitro and in vivo.

Immune tolerance mechanisms supporting normal human pregnancy are exploited by breast cancer and other malignancies. We cloned from human placenta and breast cancer cells the novel human immunomodulator named placenta immunosuppressive ferritin (PLIF). PLIF is composed of a ferritin heavy chain-like domain and a novel cytokine-like domain, named C48.

A proof of concept study: human C48-placenta immunoregulatory factor is an effective, single therapeutic agent enabling allogeneic, nonmanipulated murine bone marrow transplantation.

Objective: Cloned placenta immunoregulatory ferritin (PLIF) contains a novel, nonferritin bioactive domain (C-48) with immunodulatory activity. We documented that treatment of whole human bone marrow cells with PLIF and its subcloned C48 proteins resulted in myeloid progenitor cell growth and differentiation and T-cell suppression via an effect on the cytokine network. We tested whether this differential effect supports allogeneic bone marrow transplantation with long-lasting tolerance without any further treatments.

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.

Treatment of human bone marrow with recombinant placenta immunoregulator ferritin results in myelopoiesis and T-cell suppression through modulation of the cytokine-chemokine networks.

Objective: Placenta immunomodulator ferritin (PLIF) is a cloned human chimeric ferritin H chain with a novel non-ferritin C-terminal 48 amino acid sequence (C48). Recombinant PLIF-C48 exhibited cell-mediated immunosuppression. The aim of the current study was to investigate the regulatory effects of native placental ferritin (PLF), recombinant PLIF, and C48 on hematopoiesis of human bone marrow (BM).

PLIF induces IL-10 production in monocytes: a calmodulin-p38 mitogen-activated protein kinase-dependent pathway.

Recently, we reported the cloning and preliminary characterization of a novel human immunomodulator named PLIF (placenta immunomodulatory ferritin). PLIF has a unique molecular structure, which is composed of a ferritin heavy chain-like domain and a novel cytokine-like domain called C48. Both intact molecule and C48 inhibit T cell proliferation following allogeneic or anti-CD3 stimuli.

Placental immunomodulator ferritin, a novel immunoregulator, suppresses experimental arthritis.

Objective: To determine the effect of treatment with C48, the recombinant cytokine-like domain of the novel human placental immunomodulator ferritin (PLIF) immunoregulator, on zymosan-induced arthritis (ZIA) in mice and on adjuvant-induced arthritis (AIA) in rats.

Methods: The in vitro effect of PLIF/C48 was tested in mixed lymphocyte cultures (MLCs) of allogeneic mouse splenocytes. Arthritis was induced by intraarticular injection of zymosan into naive mice and by subcutaneous injection of Mycobacterium tuberculosis into rats.

Enhanced expression of the immunoregulator, p43-placental isoferritin, in Down's syndrome placentae and fetal kidneys.

Human placental isoferritin is composed of a 43 kDa subunit and ferritin light chains. It acts as an immunosuppressive cytokine in normal gestation and in some malignant conditions. We investigated p43-placental isoferritin expression at the maternal fetal tissue interface and in fetal kidneys in Down's syndrome (DS) compared with normal control samples.

PLIF, a novel human ferritin subunit from placenta with immunosuppressive activity.

Ferritin is a ubiquitous iron storage protein existing in multiple isoforms composed of 24 heavy and light chain subunits. We describe here a third ferritin-related subunit cloned from human placenta cDNA library and named PLIF (placental immunomodulatory ferritin). The PLIF coding region is composed of ferritin heavy chain (FTH) sequence lacking the 65 C-terminal amino acids, which are substituted with a novel 48 amino acid domain (C48).