Abstract 5241: Development of a single Listeria monocytogene-based vaccine simultaneously targeting two antigens

Abstract

Abstract Previously published studies reported that recombinant Listeria monocytogenes (Lm-LLO)-based vaccines expressing either tumor associated antigens (TAA) or angiogenesis associated antigens fused to an immunogenic fragment of listeriolysin O (LLO) have demonstrated efficacy in mouse models with several types of tumors such as lung, breast, prostate or melanoma. Therefore, we hypothesized that an Lm-LLO vaccine capable of delivering two disparate antigens with two different therapeutic mechanisms would likely have a synergistic effect on decreasing tumor growth by 1) targeting blood vessels, which may enhance effector T cell infiltration into the tumor and 2) improving the therapeutic efficacy of the vaccine. In addition, a dual vaccine construct creates a flexible platform for future use. The Lm-LLO-cHER2 vaccine was developed using a chimeric HER2/neu (cHER2) construct, and was found to regress tumors, elicit a strong T cell immune response and break immune tolerance towards the HER2/neu self-antigen in experimental animals. The Lm-LLO-VEGR2 vaccine has been shown to eradicate established breast tumors, reduce microvascular density, protect against tumor rechallange and metastases, and induce epitope spreading to various regions of the TAA such as HER2/neu. A dual Lm-LLO vaccine was developed that expresses and secretes both the VEGFR2 and cHER2 antigens as LLO-based proteins and is based on a highly attenuated Listeria monocytogenes backbone Lm Δ dal dat actA, which is cleared 48 hours post-injection in interferon gamma knock-out mice. Initial characterization of the dual vaccine indicates that the two antigens cHER2 and VEGFR2 are stably expressed and secreted after two in vivo mouse passages. Currently, we are evaluating the anti-tumor effects and antigen specific immune responses generated by the dual vaccine in mouse models. If successful, this dual vaccine may offer a new immunotherapy for the treatment of cancer in humans. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5241. doi:1538-7445.AM2012-5241