Final Program - American Society of Gene & Cell Therapy

Program Schedule, Saturday, May 18, 2013
Aliasger K. Salem, PhD
Adjuvants for Vector-Mediated Cancer Immunotherapy
This presentation will cover the use of adjuvants such as biodegradable particles and oligonucleotides to enhance the magnitude of
antigen-speciic anti-tumor CD8+ T-cell responses generated from treatment with adenovirus based vaccines. The presentation will
also discuss the use of strategies to suppress negative regulatory elements within the tumor such as myeloid derived suppressor
cells (MDSCs) and regulatory T-cells (Treg) to augment the anti-tumor activity generated by treatment with adenovirus based
vaccines.
Andrew Geall, PhD
Non-viral Delivery of Self-amplifying RNA Vaccines
Novartis has developed the SAM(tm) vaccine platform. The Platform takes advantage of cell-free RNA production from a
transcription reaction and delivery with a synthetic delivery system. The broad utility of this novel vaccine technology has been
demonstrated with genes encoding antigens from several pathogens and found to elicit broad and potent protective immune
responses. Responses are comparable to a viral delivery technology, but without the inherent limitations of viral vectors.
Scientific Symposium 433
1:45 pm - 3:45 pm
ROOM: BALLROOM D
Host Cell Responses to Viral Vectors
CO-CHAIRS: John T. Gray, PhD and Dmitry M. Shayakhmetov, PhD
SPEAKERS
Vojo Deretic, PhD
Autophagy - A Biological Paradigm for Everyone
Autophagy is a homeostatic process that continuously cleanses the cytosol by removing defunct organelles, protein aggregates,
microbial invaders, and endogenous sources of inlammation. It also supplies the cell with alternative sources of energy and
nutrients by auto-digestion of the cytoplasm during starvation. Autophagy is of signiicance in cancer, aging, neurodegeneration,
metabolic disorders, inlammatory disease such as Crohn’s disease, and infectious diseases. The presentation will cover the
pathway, its connections to disease, and focus on anti-inlammatory aspects of autophagy.
Roland W. Herzog, PhD
Innate Immunity to AAV Vectors
Rapid sensing of pathogen-associated molecular patterns by the innate immune system is a mechanism to quickly shut down
a viral infection via inlammatory responses or IFN I signaling. While a major concern for other viral gene transfer vectors,
innate responses to AAV are very short-lived and weak. Nonetheless, TLR9 sensing of the AAV genome has emerged as a critical
component of the response, and evidence for IFN I induction, induction of NF-kB and expression of inlammatory cytokines has
been obtained. Importantly, immune responses to vector and in some cases also the transgene product are impacted by innate
immunity.
Saturday, May 18, 2013
John C. Bell, PhD
Innate Immunity and Oncolytic Viruses
Oncolytic Viruses have been engineered or selected to speciically replicate in and kill tumour cells. This selectivity is often based
upon aberrant signalling pathways that are characteristic of malignant cells. However, normal cells found within the tumour
microenvironment are exposed to constitutive and elevated levels of cancer cell derived growth factors leading to a disruption of
normal which in turn can lead to overstimulation of normal cellular regulatory pathways. We have found that both neo-vascular
endothelial cells and cancer associated ibroblasts are sensitized to oncolytic virus infection and killing following exposure to
tumour cell derived growth factors. The molecular and biological consequences of this sensitization will be discussed.
Dmitry M. Shayakhmetov, PhD
Sensing of Endosomal Rupture by the Host
To achieve therapeutic beneits using gene delivery vectors, both viral and non-viral vectors must be able to eficiently
penetrate through the plasma membrane of target cells and deliver the therapeutic cargo into cytosolic and/or nuclear cellular
compartments. However, dedicated molecular sensors may exist that detect perturbations of the integrity of the plasma membrane
and endosomal compartments within the cell. When triggered, these sensors activate innate immune defense mechanisms which
can limit the eficacy of the therapy. We will review current understanding of the molecular mechanisms that are triggered within
the cell upon virus entry, and present new data on molecular sensors of adenovirus-mediated endosome rupture.
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Final Program SALT LAKE CITY, UTAH May 15–18, 2013