Abstract 586: Sera levels of the immunomodulatory protein the progesterone induced blocking factor (PIBF) are not useful in determining which patients with non-small cell lung cancer will respond to progesterone receptor modulators, e.g., mifepristone
Authors: Check Jerome H. , Check Diane , Srivastava Maya , DiAntonio Ann 
Published: August 2018

Human leukemia cancer cell line studies have demonstrated the presence of a 34 kDa intracytoplasmic splice variant of the parent 90 kDa nuclear protein associated with the centrosome that has significant immunosuppressive activity, especially, but not limited to natural killer (NK) cells. One mechanism of suppressing NK cell cytotoxicity is by stabilizing perforin granules. The 34 kDa intracytoplasmic isoform has been shown to be present only in rapidly growing cells, e.g., embryonic, mesenchymal, trophoblast, and cancer cells. During the luteal phase in ovulating women, and throughout pregnancy, there is a rise in the serum level of this immunomodulatory protein. Thus, it is called the progesterone induced blocking factor (PIBF). Interestingly, the abortafacient, mifepristone, has been shown to suppress the 34 kDa intracytoplasmic concentration of PIBF in cancer cell lines, but it does not lower serum PIBF. Based on the demonstration of significant increase in quality and length of life in controlled animal studies, and anecdotal experience in compassionate use treatment of human patients with a variety of advanced cancer types, the FDA has granted an investigator initiated salvage study of 40 patients with advanced non-small cell lung cancer (NSCLC) who have failed a minimum of two rounds of chemo or immunotherapy to be treated with single agent oral mifepristone (www.clinicaltrials.gov). The first 2 patients are doing extremely well (2 years and 1 year so far) with a high quality life without significant disease progression. Sera PIBF levels were obtained on these patients every 2 months using an experimental ELISA assay. For patient 1, a man with stage IV NSCLC with brain metastasis, his PIBF levels (ng/ml) were all in the range of normal males and women in the follicular phase (27, 38, 53, 59, 52, 46, 39, 45, 44, and 49). For patient 2, who is a female positive for the PD-L1 marker, and who progressed despite 3 rounds of chemotherapy and 1 round of nivolumab, her levels were 10, 30, 12, 21, 23, 50, 64, and 30. Thus, these results suggest that measuring serum PIBF levels in patients with very advanced NSCLC has little value in determining which patients will respond to the progesterone receptor modulator mifepristone, or be able to monitor their response to progesterone receptor modulator therapy.

Citation Format: Jerome H. Check, Diane Check, Maya Srivastava, Ann DiAntonio. Sera levels of the immunomodulatory protein the progesterone induced blocking factor (PIBF) are not useful in determining which patients with non-small cell lung cancer will respond to progesterone receptor modulators, e.g., mifepristone [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 586.