Abstract LB-318: Development of Listeria monocytogenes-based vaccine that concomitantly targets both the tumor cells as well as tumor vasculature

Abstract

Abstract Recently we described the development of Listeria monocytogenes (Lm) based chimeric human Her2/neu gene (ChHer2) harboring most of the known MHC class I epitopes of the HER2/neu oncogene (ChHer2) when expressed as a fusion protein to a non-hemolytic fragment of listeriolysin O. This construct when tested for immunogenicity and anti-tumor effects in mice proved to be efficacious in breaking immune tolerance toward the HER2/neu self-antigen and elicited strong T cell immune responses in experimental animals. These results support the further clinical development of this vaccine for treatment of HER2/neu overexpressing malignancies such as breast, colorectal and pancreatic cancers. Preclinical studies with three different Lm based vaccines targeting angiogenesis antigens have demonstrated potential in mediating the regression of tumors arising from distinct origin such as breast or skin cancer. Therefore, we hypothesized that the delivery of an angiogenic antigen simultaneously with a tumor-associated antigen will likely have a synergistic effect by impacting on tumor growth via targeting blood vessels while at the same time targeting a tumor specific antigen to enhance effector T cell infiltration in the tumor and improve the vaccine therapeutic efficacy. If true, this will result in a flexible platform by using different tumor antigens. We have created two dual recombinants Lm vaccines that express and secrete both the tumor specific antigen such as ChHer2 and tumor vasculature antigen such as High molecular weight melanoma associated antigen (HMW-MAA) successfully. Currently we are evaluating the anti-tumor effects and immune responses generated by these constructs. If successful, this study will have a great potential for human use in cancer immunotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-318.