Display options
Share it on

Clin Transl Med. 2016 Dec;5(1):32. doi: 10.1186/s40169-016-0111-8. Epub 2016 Aug 18.

Novel paradigm for immunotherapy of breast cancer by engaging prophylactic immunity against hepatitis B.

Clinical and translational medicine

Marek Malecki, Chelsea Sabo, Afsoon Foorohar, Xenia Tombokan

Affiliations

  1. Phoenix Biomolecular Engineering Foundation, San Francisco, CA, USA. [email protected].
  2. University of Wisconsin, Madison, WI, USA. [email protected].
  3. National Magnetic Resonance Facility, National Institutes of Health, Madison, WI, USA. [email protected].
  4. Sutter Health Center, San Francisco, CA, USA.
  5. University of Sheffield, Sheffield, UK.
  6. Bruker Corporation, Woodlands, TX, USA.

PMID: 27539579 PMCID: PMC4990520 DOI: 10.1186/s40169-016-0111-8

Abstract

BACKGROUND: Immunotherapy of patients suffering from the human epidermal growth factor receptor 2 overexpressing (HER-2(+)) breast cancers with the anti-HER-2 antibodies results in increase of the patients' overall survival. However, no prophylactic vaccine is available against HER-2(+) breast cancers. Although, prophylactic vaccine for human hepatitis B virus (HBV) is very effective.

SPECIFIC AIM: The specific aim of this work was to design, synthesize, and test bio-molecules which would engage prophylactic immunity against hepatitis B virus towards killing breast cancers cells.

METHODS AND RESULTS: By biomolecular engineering, we have created a novel family of biomolecules: antibody (anti-HER-2) × vaccine (HBsAg) engineered constructs (AVEC: anti-HER-2 × HBsAg). These biomolecules were utilized for redirecting, accelerating, and amplifying of the vaccination-induced, prophylactic immunity originally targeted against HBV as therapeutic immunity, newly targeted against HER-2(+) breast cancers. Treatment of the HER-2(+) breast cancer cells with AVEC: anti-HER-2 × HBsAg in blood of the patients, vaccinated with HBsAg, rapidly increased efficacy of killing of HER-2(+) breast cancer cells over that attained with the naked anti-HER-2 antibodies.

CONCLUSION: Novel antibody-vaccine engineered constructs (AVEC) facilitate redirecting, accelerating, and amplifying of prophylactic, HBV vaccination-induced immunity as immunotherapy (RAAVIIT) of HER-2(+) breast cancer. We currently streamline this novel therapeutic paradigm into clinical trials of breast and other cancers.

Keywords: Breast cancer; Cancer; Erb-B2; HER-2; Hepatitis B; Immunotherapy; Mimotope; Trastuzumab; Vaccine

References

  1. J Clin Pathol. 1976 Oct;29(10):873-9 - PubMed
  2. Sci Rep. 2014 Mar 27;4:4483 - PubMed
  3. Vox Sang. 2010 Apr;98(3 Pt 2):403-14 - PubMed
  4. Traffic. 2002 Aug;3(8):560-74 - PubMed
  5. J Biochem. 1976 Jan;79(1):233-6 - PubMed
  6. Vaccine. 2002 May 22;20(17-18):2191-6 - PubMed
  7. Semin Oncol. 1999 Aug;26(4 Suppl 12):60-70 - PubMed
  8. Science. 1987 Jan 9;235(4785):177-82 - PubMed
  9. N Engl J Med. 2004 Apr 1;350(14):1461-3 - PubMed
  10. Breast Cancer Res. 2015 Nov 17;17 :140 - PubMed
  11. Nat Med. 2004 Sep;10(9):909-15 - PubMed
  12. N Engl J Med. 2007 Jul 5;357(1):39-51 - PubMed
  13. Nature. 1982 Jul 22;298(5872):347-50 - PubMed
  14. Oncogene. 1998 Oct 29;17(17):2235-49 - PubMed
  15. Gene. 2012 Feb 1;493(1):132-9 - PubMed
  16. Cancer Epidemiol Biomarkers Prev. 2016 Jan;25(1):16-27 - PubMed
  17. Ann Oncol. 2001;12 Suppl 1:S35-41 - PubMed
  18. Cancer Treat Res. 1992;61:193-211 - PubMed
  19. Nature. 1979 Aug 30;280(5725):815-9 - PubMed
  20. Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):213-8 - PubMed
  21. Breast. 2014 Apr;23(2):128-36 - PubMed

Publication Types

Grant support