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

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.