Abstract 1567: mTERT genetic vaccine chemotherapy combination augment antigen-specific immune response and confer tumor protection in time dependent fashion

Abstract

Abstract Successful cancer chemotherapy relies on the comprehensive elimination of tumor cells. However, at clinically tolerated doses, chemotherapeutic drugs usually fail to kill all tumor cells in vivo. Theoretically, to achieve complete eradication, partial tumor killing by chemotherapy should be accompanied by a “bystander effect” in which the immune system recognizes, attacks, and eradicates residual tumor cells. Doxorubicin) is an anthracycline antibiotic that intercalates with DNA, inhibiting its replication. It has been shown that treatment of dendritic cells with Doxorubicin increases their ability to present antigen to Ag-specific T cells in vitro and it is accompanied by upregulation of the Ag-processing machinery (APM) proteins and costimulatory molecules. The telomerase reverse transcriptase, TERT, is an attractive target antigen for cancer vaccine because its expression is reactivated in a conspicuous fraction of human tumors. Critical to the success of combination therapy using TERT vaccine and chemotherapy drugs is a positive (synergistic) interaction between chemotherapy drugs and immune effectors mechanisms. Indeed, activation of antitumor immune responses by vaccine could be antagonized by chemotherapy, if the selected drug exerts immune antagonistic effects. Understanding the dose and the schedule of administration of Doxil (pegylated Doxorubicin) is critical for the design of rational combinations of vaccine and chemotherapy. To test the interactions between TERT vaccine and Doxil we performed a series of experiment using six different therapeutic schedules of Doxil/TERT administration. Interestingly, only two of the Doxil/TERT vaccine combinations resulted in a significant tumor growth inhibition delay which was also accompanied by increase in anti-TERT T cell response. This data unveil new facets of “Chemo immune adjuvancy” of Doxorubicin, and demonstrate how the in vivo efficacy of this combination is impacted by the dosing schedule 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 1567. doi:1538-7445.AM2012-1567