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
Affiliations
- Phoenix Biomolecular Engineering Foundation, San Francisco, CA, USA. [email protected].
- University of Wisconsin, Madison, WI, USA. [email protected].
- National Magnetic Resonance Facility, National Institutes of Health, Madison, WI, USA. [email protected].
- Sutter Health Center, San Francisco, CA, USA.
- University of Sheffield, Sheffield, UK.
- 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
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