9^th European Immunology Conference associated with Antibody Engineering Meeting

Despite substantial clinical progress with targeted therapies, current antibody-based approaches have limited effi cacy at controlling HER2/neu-positive breast cancers, especially in the absence of chemotherapies. Previously we showed that the combination of IFN-γ and anti-HER2/neu antibody synergistically reduces tumor growth in an in vivo implanted mammary tumor model. Here, we report a recombinant approach to produce an HER2 AbZED-IFN-γ fusion protein, which contains anti-HER2 scFv, an engineered eff ector domain (EED) scaff old, and IFN-γ, as a novel way to treat HER2+ tumors. HER2 AbZED-IFN-γ induces in vitro apoptosis in an IFN-γ receptor dependent manner. In the in vivo xenograft ed tumor model, HER2 AbZED-IFN-γ at a very low dose demonstrates superior activity over the anti-HER2/neu antibody on the growth of HER2+ tumors. In the CT26-HER2 tumor model, which is resistant to anti-HER2 antibody trastuzumab, HER2 AbZEDIFN- γ remains to show activity to inhibit tumor growth. Examination of tumor infi ltrated macrophages and lymphocytes reveals that the fusion protein can induce changes in tumor microenvironment to support immune reactivity against tumors. Furthermore, we have humanized the EED domain to minimize immunogenicity of the therapeutic protein. Our studies have defined a targeted immunotherapy approach for the treatment of cancers.