Cytokines and chemokines released from the interaction of anti-HER2/anti-CD3 bispecific antibody armed activated T cells (ATC) with the tumor microenvironment can induce efficient antigen presentation and induce an adaptive immune response

3072 Background: The tumor microenvironment has a complexes network of soluble factors, and cell surface signals which can induce a significant state of immune tolerance. Several immunotherapy strategies attempted to break this tolerance aiming to re-activate and expand tumor specific adaptive immune responses. Our approach uses ATC armed with chemically heteroconjugated bispecific antibodies (AATC) that bind and activate T cells while targeting Her2/neu on tumor targets. This creates non-HLA restricted cytotoxic/cytokine producing-T lymphocytes. Methods: Coculture experiments were perform by mixing AATC with Her2/neu+ SKBR3 target cell lines and fresh autologous peripheral blood mononuclear cells (PBMC) to induce cytotoxic activity directed at SKBR3 after 7 days. The ability of PBMCs to develop an adaptive response towards SKBR3 at the end of 7 days was studied using standard 51Cr release assay. Chemokines and cytokines released form the above interaction were studied. Results: In the presence of PBMC an...