title: Novel paradigm for immunotherapy of ovarian cancer by engaging prophylactic immunity against hepatitis B virus.
abstract: BACKGROUND
  Only eight women out of one hundred diagnosed with ovarian epithelial cancers, which progressed to the clinical stage IV, survive 10 years. First line therapies: surgery, chemotherapy, and radiation therapy inflict very serious iatrogenic consequences. Passive immunotherapy of ovarian cancers offers only low efficacy. Prophylactic and therapeutic vaccines for ovarian cancers are not available. Interestingly, prophylactic vaccines for Hepatitis B Viruses (HBV) are very effective.
  
  
  OBJECTIVE
  The specific aim of this work was to design, synthesize, and administer biomolecules, which would engage prophylactic, vaccination-induced immunity for HBV towards killing of ovarian cancer cells with high specificity and efficacy.
  
  
  METHODS
  Tissue biopsies, ascites, and blood were acquired from the patients, whose identities were entirely concealed in accordance with the Declaration of Helsinki, pursuant to the Institutional Review Board approval, and with the Patients' informed consent.
  
  
  RESULTS
  By biomolecular engineering, we have created a novel family of biomolecules: antibody × vaccine engineered constructs (AVEC: anti-HER-2 × HBsAg). We have collected the blood from the volunteers, and measured the titers of anti-HBV antibodies resulting from the FDA approved and CDC scheduled HBV vaccinations. We have acquired tumor biopsies, ascites, and blood from patients suffering from the advanced ovarian cancers. We have established cultures of HER-2 over-expressing epithelial ovarian cancers: OV-90, TOC-112D, SKOV-3, as well as human ovary surface epithelial (HOSE) and human artery endothelial (HAE) cells. Treatment of the HER-2+ ovarian cancer cells with AVEC: anti-HER-2 × HBsAg, accompanied by administration of blood drawn from patients with high titers of the anti-HBV antibodies, resulted in much higher therapeutic efficacy as compared to treatment with the naked anti-HER-2 antibodies alone and/or with the relevant isotype antibodies. This treatment had practically no effect upon the HOSE and HAE cells.
  
  
  CONCLUSIONS
  Herein, we report attaining the great improvement in eradication efficacy of ovarian epithelial cancer cells' by engaging prophylactic immunity against HBV; thus creating a novel paradigm for immunotherapy of ovarian cancer. We have accomplished that by designing, synthesis, and administration of AVEC. Therefore, the HBV vaccination acquired immunity mounts immune response against the vaccine, but AVEC redirect, accelerate, and amplify this immune response of all the elements of the native and adaptive immune system against ovarian cancer. Our novel paradigm of immunotherapy is currently streamlined to clinical trials also of other cancers, while also engaging prophylactic and acquired immunity.
  
  
  CONCLUSIONS
  Novel antibody-vaccine engineered constructs (AVEC) create the solid foundation for redirected, accelerated, and amplified prophylactic, HBV vaccination-induced immunity immunotherapy (RAAVIIT) of ovarian cancers.
authors.affiliation: Phoenix Biomolecular Engineering Foundation, San Francisco, CA, USA. mm@PBMEF.org.|University of Wisconsin, Madison, WI, USA. mm@PBMEF.org.|National Magnetic Resonance Facility, National Institutes of Health, Madison, WI, USA. mm@PBMEF.org.
authors.forename: Marek
authors.initials: M
authors.lastname: Malecki
authors.affiliation: District of Columbia, Department of Health, Washington, DC, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Putzer
authors.affiliation: Long Island University, Brookville, NY, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Quach
authors.affiliation: South Dakota State University, Brookings, SD, USA.
authors.forename: Chaitanya
authors.initials: C
authors.lastname: Dodivenaka
authors.affiliation: Bruker Bio-Spin Corporation, The Woodlands, TX, USA.
authors.forename: Xenia
authors.initials: X
authors.lastname: Tombokan