Abstract 4288: A cancer therapeutic nanoparticle vaccine targeting HAAH significantly inhibits metastasis in a mouse model of breast cancer
Authors: Fuller Steven , Lebowitz Michael , Stewart Solomon 
Published: August 2015

Abstract
We are evaluating the efficacy of a nanoparticle vaccine targeting the tumor marker Human aspartyl (asparaginyl) β-hydroxylase (HAAH) in a mouse model of breast cancer. HAAH is over-expressed on the surface of cancer cells and is contained in the exosome fraction of the serum. It is an embryonic protein that is demonstrated to be responsible for cancer etiology: cell proliferation, motility and invasiveness. When normal cells are transfected to over-express HAAH they behave as transformed and when HAAH is neutralized or its expression is inhibited, cancer cells regain a normal phenotype. Anti-HAAH antibodies inhibit cancer cell growth, motility and invasiveness in vitro, and inhibit tumor growth in vivo. We have developed a novel anticancer nanoparticle vaccine in which the N-terminal or C-terminal thirds of HAAH are expressed on λ-phage (200-300 copies). These anticancer vaccines are immunogenic and produce high-titer anti-HAAH polyclonal antibodies in mice. The HAAH gene is highly conserved between mice and humans. We have previously shown in several studies that vaccination with the nanoparticles inhibits tumor growth and metastasis in a mouse liver cancer model. The vaccine generates and works through both humoral and cellular responses. The current study used the mouse 4T1 triple-negative breast cancer cell line to further study the effects of the nanoparticle vaccine on metastasis. Female BALB/c mice (groups of 8 animals each) were immunized with 10E09 or 10E10 phage particles displaying the N-terminal (HAAH-1λ) or C-terminal (HAAH-3λ) thirds of HAAH. A control group received the parent λ-phage, not displaying any HAAH sequences. Immunizations were performed on days 1, 8 and 22. Mice were injected with 2×104 4T1 breast cancer cells subcutaneously into the mammary fat pad on day 15. The volumes of primary mammary tumors were measured twice per week through the study and the mice were sacrificed on day 43 to collect the lungs for determination of the number of metastatic foci. Sera from the animals were collected on day 15 and 43 to assess the antibody response to the vaccines. Our results indicated that both vaccines were immunogenic. The growth of solid tumors in the mammary glands was inhibited by 28 to 46% in vaccinated animals compared to the control group. More importantly, the number of lung metastases was reduced by 62 to 78% (p&lt;0.01) in the vaccine groups given 109 nanoparticles compared to the control group. These data provide evidence that a nanoparticle vaccine targeting HAAH is effective in inhibiting tumor growth and metastasis in this mouse model of breast cancer and that this vaccine overcomes some of the hurdles to cancer vaccine development.
Citation Format: Steven Fuller, Michael Lebowitz, Solomon Stewart. A cancer therapeutic nanoparticle vaccine targeting HAAH significantly inhibits metastasis in a mouse model of breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4288. doi:10.1158/1538-7445.AM2015-4288