A model for potential tumor immunotherapy based on knowledge of immune mechanisms responsible for spontaneous...

Attempts to treat various cancers by immunotherapy have been tried for about 50 years. Most studies have focused on improving cytotoxic T lymphocyte (CTL) responses against various tumors. Immunotherapy has been both active and passive, and results have been modest at best. Spontaneous abortion (SAB) of pregnancies could in some ways resemble remission of a tumor. Both tumors and conceptusses are faced with a similar problem -- how to grow in a host in a vascular rich area, and yet escape immune surveillance despite both entities being an allogenic stimulus. In general, the fetus is far more immunogenic than a spontaneous tumor, and yet abortuses seem to avoid CTL responses but are sometimes invaded by natural killer (NK) cells. There are data suggesting that SAB will occur if there is inhibition of production of an immunosuppressive protein called progesterone-induced blocking factor (PIBF). This protein inhibits NK cell cytolysis and influences TH2 cytokine dominance over TH1. If some tumors avoid NK cell destruction through a PIBF mechanism, perhaps an active rejection of these tumors could be achieved by inhibiting PIBF production by treating with a progesterone receptor antagonist. Passive immunization could also be considered by conjugative radionuclide or toxic chemical to a PIBF antibody which may be tumor specific since PIBF is not produced in normal tissue. The first step should be to see if PIBF can be detected in the peripheral circulation in patients with certain tumors.