The Pre-Clinical Assessment of the Anti-Tumor Efficacy of a Protein Vaccine and Mesenchymal Stem Cell Combined Therapy, Using Non-Invasive Molecular Imaging Technology

Previously, a protein vaccine specifically against E7 antigen, PE(ΔIII)-E7-KDEL3, was developed by our collaborators and shown to be effective against cervical cancer in a mouse model. Although effective, this vaccine is limited to E7 antigen expressing tumor types. In this application, we propose to expand the usage of this vaccine to all cancer types by adding another component, E7 antigen expressing mesenchymal stem cells, Kp-hMSCs. We showed that Kp-hMSCs targeted and infiltrated tumor without becoming tumorigenic. By combining these two components termed PV-MSC, we preliminarily demonstrated its efficacy in reducing subcutaneous tumor burden in mice. We aim to accomplish the following goals. First, the efficacy of this PV-MSC therapy in a pulmonary metastatic mouse model will be assessed with the aid of non-invasive molecular imaging technology. Second, the generality of our PV-MSC system will be tested in different tumor models. In addition, Kp-hMSCs’s function will be improved by the incorporation of triple reporter system for nuclear (HSV1-Tk, also a suicide gene), fluorescence (GFP) and bioluminescence (luciferase) imaging purposes, thus termed Kp-hMSC-TGL. Importantly, the anti-tumor effect of Kp-hMSC-TGL mediated immune response can be further enhanced by Tk/GCV(ganciclovir) induced Kp-hMSC-TGL cellular suicide thereby increasing the tumor killing efficiency. Finally, the underlying immunological pathways mediated by PV-MSC treatment will be delineated. Equally important, the intricate cancer-stem cell interactions will also be investigated. The successful completion of this proposal would provide important experimental evidence for the clinical translation of this methodology and further our understanding in the fields of cancer immunology.