Abstract 233: Therapeutic efficacy of cancer stem cell-based vaccine in an adjuvant setting.

Abstract

Abstract So far, the majority of cancer stem cell (CSC) studies have been confined to human tumors inoculated into severely immunosuppressed hosts (e.g. SCID mice), where adaptive immune responses are absent, and such hosts are therefore not suitable for the immunologic evaluation of CSCs. The lack of immunocompetent syngeneic animal tumor models where stem cells can be isolated has been the primary obstacle to evaluating the immunogenicity of CSCs. We recently reported the identification of CSC-enriched populations using ALDEFLUOR/ALDH as a marker in murine melanoma D5 and squamous cell cancer SCC7, and evaluated their immunogenicity in two genetically distinct syngeneic immunocompetent hosts. Enriched CSCs are immunogenic and significantly more effective as an antigen source in inducing protective anti-tumor immunity than unsorted tumor cells or purified non-CSCs. We further found that selective targeting of CSCs by CSC-primed antibodies and T cells represents the mechanisms involved in CSC vaccine-conferred protective immunity. If a CSC vaccine is to be clinically relevant, it needs to be evaluated in a therapeutic model. In this study, we examined two models for this purpose. The first model involves the treatment of micrometastatic disease. We initiated vaccination 24 hrs after s.c. inoculation of D5 tumor cells in the syngeneic immunocompetent host (B6 mice), and repeated the vaccination one week later. Comparison was made among the group with PBS-injected controls; mice vaccinated with dendritic cells (DC) pulsed with the lysate of ALDHhigh D5 cells (CSC-TPDC) vs. ALDHlow D5 cells (ALDHlow -TPDC). We found that CSC-TPDC inhibited the tumor growth more than ALDHlow-TPDC and PBS controls, and significantly prolonged the survival of the tumor-bearing mice. The second model involves the treatment of established tumors using CSC-TPDC vaccine as an additional strategy to radiation therapy (RT). Day 7 D5 sc tumors were treated with localized RT with repeat treatments on D8. Vaccine therapy commenced on D8. This combination therapy was repeated twice with one week apart. CSC-TPDC plus RT mediated D5 tumor regression more than ALDHlow-TPDC + RT, RT alone and PBS controls, and prolonged the survival of the tumor-bearing mice. Importantly, we observed metastasis of the D5 tumors to the lung in all the groups except for the one treated with CSC-TPDC plus RT. The findings may help develop novel approaches for cancer treatment by utilizing an autologous cancer stem cell-based vaccine to selectively and immunologically target cancer stem cells. Citation Format: Lin Lu, Huimin Tao, Martin Egenti, Max S. Wicha, Alfred E. Chang, Qiao Li. Therapeutic efficacy of cancer stem cell-based vaccine in an adjuvant setting. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 233. doi:10.1158/1538-7445.AM2013-233