Antiangiogenic and antitumoral therapy delivered by a dual-expression L. monocyto

DESCRIPTION (provided by applicant): Breast cancer is the second most common type of cancer in females, causing over 40,000 deaths in the United States annually. Recently, cancer vaccines have arisen as a potential therapy and several target antigens have been identified in Breast cancer, including Her2/neu antigen. The goal of cancer vaccines is to generate effector T cells that are able to infiltrate and kill the tumor cells. We propose to generate a single recombinant Listeria monocytogenes capable of targeting cancer cells and tumor vasculature by concomitant expression of Her2 and HMW-MAA, which is expressed in pericytes and plays a role in tumor angiogenesis. To address this challenge, a dual-expression Lm platform is created by expressing Her2 from the chromosome and HMW-MAA from a plasmid. To enhance immunogenicity, both antigens are fused to the virulence factor listeriolysin-O and immune responses and therapeutic efficacy of the dual-expression system will be evaluated, including analysis of tumor-infiltrating lymphocytes and tumor vasculature. Delivery of an anti-angiogenic antigen simultaneously with a tumor-associated antigen will likely have a synergistic effect in impacting tumor growth by targeting blood vessels, which might enhance effector T cell infiltration in the tumor and improve the vaccine therapeutic efficacy, besides creating a flexible platform for future use. PUBLIC HEALTH RELEVANCE: Breast cancer is a major health problem in female population, causing the death of over 40,000 American men annually. In this SBIR Phase I project, Advaxis Inc. will construct a novel, clinically suitable recombinant Listeria monocytogenes capable of targeting Her2 expressing breast cancer cells and tumor vasculature concomitantly, which will be tested in a mouse tumor model.