FINAL PROGRAM - American Society of Gene & Cell Therapy

56American Society of Gene & Cell TherapyProgram ScheduleEvan Y. Snyder, MD, PhD, FAAP“Lineage Mapping” The Development of a Brain TumorCarl Bart Rountree, MDThe Role of Stem Cells and Cancer Stem Cells in Liver CancerHepatocellular carcinoma (HCC) ranks as the third most frequent cause of cancer-related mortality in the world; and over the last four decades, traditional cytotoxicchemotherapy has failed to improve patient survival in HCC. Typically, patients develop HCC after many years of chronic liver injury, during which time, there is a significantexpansion of the liver stem cell pool. Increasing evidence indicates that liver cancer stem cells (CSC) are the origin of a subset of HCC, and patients with a CSC phenotypeHCC have a significantly worse prognosis. Additionally, using stem cell surface markers such as CD133, purified liver CSC populations have been identified within humanHCC cell lines and mouse models that mimic human chronic liver injury and HCC development. These liver CSCs are resistant to traditional chemotherapy agents andligand-receptor mediated apoptosis, form tumors at very limited dilution, and represent a critical therapeutic target in future HCC treatments.Friday, May 21 stScientific Symposium 31210:30 am - 12:30 pmRoom: Thurgood Marshall WestCurrent Status of Genetic VaccinesChairStephen Gottschalk, MDSpeakersSi-Yi Chen, MD, PhDDC-based Tumor Vaccine by Combining SOCS1 Silencing and TLR SignalingMichael A. Barry, PhDGene-based Vaccines Against Mucosal PathogensThe vast majority of pathogens enter the body at mucosal surface. Yet, most vaccine strategies are delivered into the systemic immune system where induced immunologicalmemory may not efficiently “cross-over” to mucosal surfaces to provide barrier protection against these pathogens. To maximize protection, we will discuss comparisonsof replication-competent and replication-defective first generation and helper-dependent adenoviral vaccines for their utility in systemic and mucosal infections by SHIV,influenza, and methicillin-resistant Staphylococcus Aureus (MRSA). We will also discuss “stealth” strategies during vaccination to evade pre-existing and vector-inducedimmunity against adenovirus including serotype-switching and PEGylation.Sattva S. Neelapu, MDTargeting Chemokine Receptors with Fusion DNA VaccinesTherapeutic vaccination with patient-specific tumor-derived idiotype protein conjugated to a carrier molecule, keyhole limpet hemocyanin and administered with granulocyte-monocytecolony-stimulating factor as an adjuvant was shown to induce tumor-specific immune responses and molecular remissions in follicular lymphoma patientsin phase II clinical trials. Results from a recently completed randomized controlled double-blind phase III trial suggested that administration of idiotype protein vaccine inthe setting of minimal residual disease improves disease-free survival in patients with follicular lymphoma as compared with control. However, a major limitation of thisstrategy is the requirement to generate a custom-made protein vaccine for each patient, by a process that is expensive, laborious, and time-consuming. DNA vaccines maybe produced more rapidly and provide an alternative to protein vaccines. Strategies to enhance the efficacy of DNA vaccines by fusing tumor antigens to chemokines andusing novel adjuvants will be discussed.Stephen Gottschalk, MDAdenoviral Vaccines for Enhancing T-cell Therapies for CancerAlthough the benefits of T-cell therapy for cancer can be increased by prior lymphodpeletion of the host, this process has usually required chemotherapy or radiation.Vaccination with tumor associated antigens to which the transferred T cells respond should be a less toxic means of promoting antitumor activity, but to date this hasproved ineffective, favoring instead the transition to a non-cytotoxic immune response. We have developed a new adenoviral based vaccine that contains antigen, atoll-like receptor 5 activator and an inhibitor of the antigen presenting attenuator A20. Administration of this vaccine prior to T-cell transfer induces a strong Th1-polarizingenvironment leading to potent antitumor effects even in the absence of lymphodepletion and even when vaccination or T-cell transfer alone are ineffectual. Such Th1-polarizing vaccines may be of value when enhancement and maintenance of a Th1 response is desirable.EXHIBITOR PROSPECTUSfinal program