Immunization with E1A expressing tumor cell line enhances antigen specific tumor immunity (74.5)

Abstract

Abstract The stable expression of Adenovirus (Ad) E1A in tumor cells reduces tumorigenicity by 1,000 fold, an effect dependent on the elicitation of an NK cell and T cell mediated antitumor response. We generated B6 fibrosarcoma cell lines (MCA tumor cells) that stably expressed ovalbumin (MCA-OVA) or full-length E1A fused to ovalbumin (MCA-E1A-OVA) to test the hypotheses that E1A could function as a molecular adjuvant to induce a robust anti-tumor immune response to other weakly or non-immunogenic tumor antigens. MCA E1A-OVA was more susceptible to killing by NK in vitro and 1000 fold less tumorigenic than MCA or MCA-OVA in vivo. Immunization with 1X10^5 live MCA-OVA or MCA- E1A-OVA tumor cells elicited comparable numbers of IFNγ- and TNFα -producing OVA specific CD8 T cells that had similar cytolytic activity against OVA-expressing target cells in in vivo CTL killing assays. Immunization of MCA-OVA or MCA-E1A-OVA cells also increased the number of MCA-OVA cells required to form tumors by 1,000 fold in an anatomically distant site. However, primary tumors developed at the site of immunization with MCA-OVA but not MCA-E1A-OVA cells. These data demonstrate that immunization of live MCA-E1A or MCA-OVA tumor cells can elicit a robust, systemic anti-tumor immune response. However, primary tumor progression occurs at the site of inoculation following immunization with MCA-OVA cells despite the induction of an anti-tumor immune response.