Detailed Program Schedule
Thursday, May 29
8:00 am - 9:15 am
Room Ballroom A-C
Chair
David M. Bodine, PhD
Speaker
Francis S. Collins, MD, PhD
Genomics, Medicine, and Society
The completion of all of the goals of the Human Genome Project in April 2003 marks an inflection point in the approach to solving biological mysteries. In the past, rather like the man who lost his keys late at night, we have been forced to “look under the lamppost” to try to determine mechanisms of health and disease. Genomics provides the opportunity for comprehensiveness, and thus allows the whole street to be illuminated. The exponential acquisition of publicly accessible datasets on genome sequences, comparative genomics, genome functional elements, genetic variation, and gene expression has provided an unprecedented opportunity to answer fundamental questions about biology that were previously out of reach. The implications for the practice of medicine -- in diagnostics, preventive medicine, pharmacogenomics, and therapeutics -- are potentially profound, but many of these benefits will require many years of dedicated research effort to realize.
Presentation of Excellence in Research Awards
9:30 am - 11:30 am
Room 304 - 306
Chair
John G. Hay, MD
Speakers
John G. Hay, MD
Modulation of the Microenvironment to Augment Viral Vector Gene Therapy
The ability of a lytic replicating virus to multiply several hundred-fold within an infected cell, and then spread from infected-to-uninfected cells in repeated waves of infection holds considerable promise for the treatment of solid tumors. The tumor milieu, however, is a problem for therapy. Tumors are complex tissues of several different cell types, both malignant and non-malignant, within a matrix lattice. The centers of tumors are often hypoxic, acidic, with poor blood flow and high interstitial pressures. For virotherapy to be effective, the physical problems of the matrix stroma, and the hypoxic conditions within tumors need to be addressed. Strategies to improve the outcome of virotherapy include matrix modification and modulation of angiogenesis.
Andre Lieber, MD, PhD
Tumor-Localized Immuno-Gene-Therapy
We tested a number of immuno-gene therapy approaches in a mouse model of breast cancer that involves neu-transgenic mice and syngeneic mouse mammary carcinoma cells. We showed that tumor-localized expression of the peptide hormone relaxin results in fragmentation of tumor stroma and facilitation of anti-tumor immune responses. Furthermore, we demonstrated that tumor-localized expression of immuno-stimulatory molecules, such as anti-CTLA4 or anti-CD3 antibodies, can induce tumor-destructive immune responses without auto-immunity. To achieve tumor-localized transgene expression, we pursued two approaches: i) injection of tumor-targeted adenovirus vectors and ii) transplantation of genetically modified, tumor-homing hematopoietic stem cells.
Steven M. Albelda, MD
TGF-Beta Blockade to Augment T-Cell Adoptive Transfer
One major impediment to successful immunogene therapy is the production of cytokines, like TGF-β, that create an immunosuppressive tumor micro-environment. We hypothesized that inhibition of TGF-β would augment the efficacy of three types of immunotherapy: intratumoral injection of an adenovirus expressing IFN-β (Ad.IFN β ), an adenoviral cancer vaccine, and adoptive transfer of lymphocytes. TGF-β effects were inhibited by administering SM16, a novel, orally available, small molecule TGF-β type I receptor kinase inhibitor (from BiogenIdec) to animals bearing large flank tumors. In all three models, treatment efficacy was markedly enhanced. The primary mechanism appeared to be an alteration of the tumor microenvironment favoring upregulation of immunostimulatory chemokines, cytokines, and endothelial cell adhesion molecules. This led to increased numbers and increased activation of CD8 cells within the tumors. Thus, blockade of the TGF-β signal pathway should be considered for use in clinical immuno- and immunogene therapy trials.
John C. Bell, PhD
Oncolytic Virus Therapy of Cancer
Intra-tumoural innate immunity can play a significant role in blocking the effective therapeutic spread of a number of oncolytic viruses (OVs). Histone deacetylase inhibitors (HDIs) are known to influence epigenetic modifications of chromatin and can blunt the cellular, anti-viral, interferon response. We reasoned that pre-treatment of tumours with HDIs could enhance the replication and spread of OVs within malignancies. Here we show that HDIs markedly enhanced the spread of three distinct OV platforms in a variety of cancer cells in vitro, in primary tumour tissue explants and in animal models. These results illustrate the general utility of HDIs as chemical switches to regulate cellular innate anti-viral responses and provide controlled growth of therapeutic viruses within malignancies. HDIs could have a profound positive impact on the clinical implementation of oncolytic virus therapeutics.
9:30 am - 11:30 am
Room 311
Chair
Duncan J. Stewart, MD, FRCPC
Speakers
David T. Curiel, MD, PhD
Genetically Induced Retargeting of Meschymal Stem Cell Vehicle for Effective Delivery of Adenovirus Virotherapy Agents
Duncan J. Stewart, MD, FRCPC
Cell-Based Gene Therapy for the Lung
Lung diseases represent an important target for gene therapy approaches, however, success has been limited by efficiencies of targeting and transfection. We have developed a cell-based approach to target gene transfer to the arterial or microvasculature of the lung. Pre-clinical studies will be presented to validate the efficacy and safety of this approach using somatic and progenitor cells for the treatment of pulmonary hypertension and acute lung injury. As well, an update of the ongoing Pulmonary Hypertension and Cell Therapy (PHACeT) trial, which is studying the effects of genetically enhanced endothelial progenitor cells for the treatment of patients with idiopathic pulmonary arterial hypertension.
Michael Andreeff, MD, PhD
MSC - Delivered Anti-Tumor Therapy
Clive Svendsen, PhD
Using Stem Cells to Deliver Growth Vactors in Neuro Degenerative Diseases
9:30 am - 11:30 am
Room 100
Chair
David B. Weiner, PhD
Speakers
Susan W. Barnett, PhD
Recombinant Alphavirus Replicon Vector Vaccines for HIV
The primary objective of our current HIV vaccine research program is to evaluate novel alphavirus replicon particle and Envelope (Env) protein-based vaccine formulations against HIV that may offer improved immunogenicity and efficacy over other HIV vaccine approaches. A chimeric alphavirus vector system (VEE/SIN) was used that is composed of the Venezuelan Equine Encephalitis (VEE) replicon combined with the Sindbis (SIN) virus structural proteins. Recombinant VEE/SIN particles expressing HIV antigens were evaluated alone or in combination with novel Env protein formulations composed of trimeric Env protein vaccines in various animal models including rhesus macaques. Protection of macaques from mucosal challenge with SHIV was seen using both alphavirus prime-Env protein boost and adjuvant protein vaccine approaches. Protection in this model appeared to correlate with the induction of high avidity binding antibodies and high titer serum neutralizing antibodies that recognized the challenge virus. Future studies will focus on protection against heterologous challenge viruses using these vaccine technologies.
Ruxandra Draghia-Akli, MD, PhD
“Shocking” Immune Therapies by Electroporation
Within the last decade, electroporation has evolved from an experimental technique derived from in vitro applications to a robust pre-clinical and clinical delivery method of nucleic acids and other macromolecules. This physical method for in vivo non-viral gene therapy and vaccination is currently used in laboratory animals, large mammals and human clinical trials with significant successes, especially when optimized expression cassettes and novel formulations are used. The current presentation will review our studies in different models, such as human immunodeficiency virus, influenza, human papilloma virus and small pox showing robust immune responses, and/or protection from challenges in large mammals after intramuscular or intradermic administration of optimized DNA vaccine formulations by electroporation.
James M. Wilson, MD, PhD
DNA Viruses as Vaccine Carriers
Viral vectors have been used for the majority of gene therapy and genetic vaccine studies. An important aspect of their biology that impacts on performance is the response of the host to the vector and vector transduced cells. It has become clear that previous exposure of the host to the virus (or a related virus) on which the vector was made can impact substantially on vector safety and efficacy. Previous studies have focused on the role of pre-existing humoral immunity although memory T cells to vector may also play a role. This talk will review studies directed towards the study of AAV and Ad specific memory T cells on vector biology.
Michael Robertson, PhD
Results from the STEP Study: A TOC Study with the MRKAd5 HIV-1 Vaccine
Background: Thus far, efforts to develop HIV vaccines capable of eliciting broadly cross-reactive neutralizing antibodies have been unsuccessful; therefore, much recent attention has focused on vaccine-induced HIV-specific cell mediated immune (CMI) responses. Such vaccines have shown partial success in some animal models, but this concept has not been previously tested in humans. Methods: A collaborative study between Merck, the HVTN, and NIH was initiated in 2004. The study is a phase II, randomized, multi-center, double-blind, placebo-controlled test-of-concept study in 3000 HIV seronegative volunteers at high risk of acquiring HIV. Volunteers were randomized (1:1) to receive 3 injections of either the MRKAd5 HIV-1 gag/pol/nef vaccine (a replication defective Ad5 vector) or placebo. Volunteers were tested every 6 months for acquisition of HIV. In volunteers who became HIV infected, viral load and CD4 cell counts were measured at multiple timepoints post-diagnosis. Results: In volunteers with low (< 200) baseline Ad5 neutralizing antibody titers (the primary analysis population), there were 24 infections among the 741 vaccinees compared to 21 infections among the 762 placebo recipients (using a modified intent-to-treat approach), and among the volunteers who became HIV infected, the geometric mean plasma vRNA level was 40,000 copies/mL in the vaccine group compared to 26,000 copies/mL in the placebo group. Lack of efficacy did not appear to be explained by lack of immune responses in vaccinees. Post-hoc analyses demonstrated that the trend towards more infections in the vaccine group was more pronounced in volunteers with high (>200) baseline Ad5 titers (21 infections in 392 vaccinees vs. 9 in 386 placebo recipients). Viral loads were similar between the two treatment groups in the high Ad5 stratum. Conclusions: There was no evidence that vaccination prevented infection or lowered viral setpoint; in fact, there were more infections in the vaccine group. Investigations are under way to try and determine if these results are explained by immune responses induced by the vaccine (either to the transgenes or to the vector itself), by differences in the study populations (e.g., behavioral differences, HLA, HSV-2 serostatus, etc) or, since the numbers are relatively small, simply due to chance. Because of the implications for the development of other CMI based vaccines, it will be important to understand the potential mechanisms underlying these results.
9:30 am - 11:30 am
Room 309
Chair
John Iacomini, PhD
Speakers
Dwight Koeberl, MD, PhD
Immunomodulatory Gene Therapy in Pompe Disease: Immune Tolerance Mediates the Efficacy of Enzyme Replacement Therapy
Infantile Pompe disease (MIM 232300) is caused by the deficiency of lysosomal acid alpha-glucosidase (GAA; acid maltase; EC 3.2.1.20), and, if untreated, results in early death from cardiorespiratory failure. Enzyme replacement therapy (ERT) with recombinant human GAA improved overall survival, ventilator-free survival and cardiac function; however, patients that lacked any residual GAA expression mounted a robust antibody response to ERT and declined clinically. Preclinical studies with an adeno-associated virus vector containing a liver-specific promoter enhanced the efficacy of ERT, when administered prior to initiation of ERT to prevent the antibody response in GAA knockout mice. Adeno-associated virus vector mediated gene therapy induced immune tolerance to introduced GAA, and this strategy could prevent antibody responses to ERT in Pompe disease and in other lysosomal storage diseases.
John Iacomini, PhD
Marginal Zone B Cell Responses and Tolerance
Natural antibodies play a major role in providing protective host immunity. The specificity of many natural antibodies remains undefined, however, a significant portion is specific for carbohydrates such as blood groups antigens. In addition to anti-ABO blood group antibodies, natural antibodies specific for a carbohydrate antigen Gal1-3Gal-4GlcNAc-R, hereafter referred to as Gal, represent a significant population of natural antibodies. To study anti-carbohydrate B cells we generated immunoglobulin knock-in mice that carry functionally rearranged heavy and light chain variable region genes isolated from a B cell hybridoma producing Gal specific IgM antibody. These mice allowed us to examine the development of B cells producing anti-carbohydrate natural antibodies in the presence or absence of Gal as a self-antigen. Knock-in mice on a Gal deficient background spontaneously developed Gal specific IgM antibodies of a sufficiently high titer to mediate rejection of Gal expressing cardiac transplants. In the spleen of these mice, B cells expressing Gal specific IgM were located in the marginal zone. In knock-in mice that express Gal, B cells expressing the knocked-in B cell receptor (BCR) underwent negative selection via receptor editing. Interestingly, production of low affinity Gal specific antibody was observed in mice that express Gal that carry two copies of the knocked in heavy chain. We suggest that in these mice, receptor editing functioned to lower the affinity for self-antigen below a threshold that would result in overt pathology, while allowing development of low affinity anti-self antibodies. The implications of these results for tolerance induction as it relates to gene therapy will be discussed.
John C. Cambier, PhD
Silencing Autoreactive B Cells by Anergy; Physiologic Importance and Molecular Underpinning
Success of gene therapy involving “foreign” protein expression is dependent upon induction of immunologic tolerance to the ectopically expressed protein. To accomplish this tolerance it will be necessary to understand molecular processes that normally maintain unresponsiveness to self. Based on this knowledge we can manipulate operative mechanisms to accomplish unresponsiveness to the ectopically expressed protein. This presentation will focus on molecular mechanisms that maintain the tolerance of anergic B cells, and how they might be manipulated in gene therapy.
David W. Scott, PhD
B Cell-Delivered Gene Therapy for Tolerance Induction
During the past decade, we developed a gene therapy model based on the use of immunoglobulin carriers and B-cell antigen presentation to achieve specific T-cell tolerance. Novel tolerogenic vectors expressing these “fusion Ig’s” are delivered to B cells which can then be used to achieve antigen-specific tolerance. This model has been used successfully with over a dozen antigens, and shown clinical efficacy in pre-clinical animal models for diabetes, MS, uveitis and hemophilia. In preparation for eventual translation to human gene therapy, we discovered that the mode of activation of the B cell was critical for tolerance induction. In this presentation, I will review the basis of our approach, provide some mechanistic insights and present new data on the interactions of tolerogenic B cells with target T cells in vivo. (Supported by NIH grants AI035622, DK068343 and HL061883).
9:30 am - 12:00 pm
Room 302
Chair
Douglas J. Jolly, PhD
Speakers
Daniel Gaudet, MD, PhD
Safety, Efficacy and Clinical Consequences of Intramuscular Administration of AMT-011, an Adeno-Associated Viral Vector Expressing Human Lipoprotein LipaseS447X in Patients with Severe Hypertriglyceridemia
Robert L. Engler, MD
The First Phase III Trial of: Angiogenesis in Women with Angina pectoris who are not candidates for REvascularization (AWARE)
Preclinical studies with intracoronary administration of Ad5FGF-4 (alferminogene tadenovec) suggested it could augment angiogenesis and provide a new clinical approach to the treatment of myocardial ischemia in patients with recurrent or refractory angina. The four AGENT trials (663 patients, 450 active treatment) demonstrated safety, and a by-patient pooled analysis of ETT results from the nearly identical AGENT 3 and 4 trials of a low and high dose of Ad5FGF-4 versus placebo (1:1:1 randomization) for chronic angina found that: 1) the placebo effect in men was large and no significant difference between the groups was discernible (n=417), but 2) the placebo effect in women was negligible and the treatment effect was significantly greater than placebo (n=72, prespecified analysis). There was a statistically significant, female gender-specific beneficial effect of Ad5FGF-4 on total ETT time (primary end point), time to 1 mm ST-segment depression, and Canadian Cardiovascular Society class (secondary end points) that was sustained at 6 months of follow up (J Am Coll Cardiol 2007;50:1038–46). Accordingly the Phase 3 AWARE study of Ad5FGF-4 in women age 18-75 with stable angina CSS class 3 or 4 who are not candidates for, or not likely to benefit from, standard revascularization procedures, has been initiated and will enroll up to 300 patients at 50 sites. The FDA and Cardium agreed on: 1) the primary approvable end point of time to 1 mm ST depression (not total ETT time) at 6 months after treatment, to reflect the potential underlying disease-modifying effect on myocardial ischemia, 2) the key secondary end point of stress inducible, reversible myocardial ischemia on SPECT which may confirm a disease-modifying effect and serve as a possible surrogate end point in future studies, and 3) Fast Track designation to the Ad5FGF-4 development program to address the serious unmet medical need of patients with recurrent angina. www.clinicaltrials.gov/ct/show/NCT000438867 .
Mark O. Thornton, MD, MPH, PhD
Clinical Development of TNFerade as an Anticancer Therapeutic
TNFerade is a replication-deficient adenovector containing the human Tumor Necrosis Factor Alpha (TNF-α) gene, regulated by the chemoradiation-inducible promoter, EGR-1. Once injected into a tumor, the vector distributes and integrates, and following radiation or chemotherapy stress, TNF-α is produced in local pharmacologic doses. The product demonstrated significant local anti-cancer activity during its Phase I development program, and GenVec subsequently embarked on Phase 2 programs in several cancer types. The farthest along is the Phase 3 program in pancreas cancer, and the status of the pivotal registration trial for this beachhead indication will be discussed. In addition, recent progress in both the esophageal and head and neck cancer Phase 2 trials will be discussed.
Jean-Yves Bonnefoy, PhD
Tageted Immunotherapy
Therapeutic vaccination against cancer and infectious diseases-associated antigens represents a new option for therapy in view of its combination with other treatment modalities, the possibility of long lasting immunity against the disease and the safety profile. Moreover, it is now recognized that the same vaccination strategies used for prophylactic vaccinations against infectious diseases, cannot necessarily be used for therapeutic vaccination. Such patients are usually immunosuppressed and most cancer-associated antigens are ‘self-antigens’. Therefore various immunostimulation technics are under investigation in an effort to bolster the patients immune system and to overcome immune tolerance to self antigens. Most recent clinical data will be presented.
John J. Nemunaitis, MD
Efficacy of Adenoviral p53 Gene Therapy (Advexin) in Pivotal Clinical Trials for Recurrent Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Adenoviral p53 gene therapy (Advexin) administered by local intratumoral injection was evaluated for efficacy and safety in two pivotal clinical trials involving 235 patients with recurrent SCCHN. Biomarkers of the p53 target of Advexin therapy predicted Advexin efficacy and identified patients most likely to benefit from Advexin treatment with increased tumor responses and survival. Biomarker profiles predictive of Advexin efficacy were based upon p53 gene configurations assessed by sequence analyses and their level of protein expression determined by immunohistochemistry. The absence of high level protein expression of “dominant negative” p53 mutations that can block Advexin activity were predictive of Advexin efficacy.
There was a statistically significant correlation between p53 profiles favorable for Advexin efficacy and tumor growth control responses following Advexin treatment. An integrated analysis of p53 biomarker data from recurrent SCCHN patients treated with Advexin monotherapy in Phase 1, 2 and 3 clinical trials revealed that a tumor growth control response was observed in 79% of patients with p53 profiles favorable for Advexin efficacy compared to only 25% of patients with unfavorable profiles (p = 0.004 by Fisher’s Exact Test). In the Phase 3 clinical trial, there was a highly statistically significant difference in survival outcomes by logrank analysis (p = 0.0001) for patients treated with Advexin or methotrexate based upon p53 biomarker profiles that were favorable or unfavorable for Advexin efficacy. The median survivals for these populations ranged from 7.2 months for patients with p53 profiles predictive of Advexin efficacy who were treated with Advexin compared to only 2.7 months for patients with profiles unfavorable for Advexin efficacy receiving Advexin treatment (p < 0.0001). Intermediate median survival times were observed for the patients with profiles favorable and unfavorable for Advexin efficacy treated with methotrexate (4.3 and 5.9 months respectively). Advexin was found to have a superior safety profile compared to methotrexate. There was no statistical difference in median survival for the methotrexate treated patients based upon p53 profiles predictive of Advexin efficacy. However, patients with p53 profiles unfavorable for Advexin efficacy had a statistically significant increase in survival when treated with methotrexate (median survival 5.9 months vs. 2.7 months, p = 0.0112).
These data indicate that Advexin and methotrexate are efficacious in complementary patient populations and that p53 biomarkers predictive of Advexin treatment effects provide important information to direct the future use of these therapies in patients with recurrent SCCHN.
9:30 am - 11:30 am
Room 112
Co-Chairs
John J. Rossi, PhD
Anton P. McCaffrey, PhD
Speakers
Phillip A. Sharp, PhD
Gene Silencing by Small RNAs
The discoveries of RNA interference and microRNAs provide general methods to silence any target gene in mammalian cells. Small RNA can be designed to be complementary to a disease gene and introduced as either a DNA vector or as RNA directly. Optimal sequences can silence with efficiencies of 20 fold with negligible off target effects. Vectors expressing small RNAs have been introduced in the germline for specific silencing or into somatic cells directly. The science and examples of gene silencing by RNA interference and microRNAs will be discussed.
Christopher Burge, PhD
Systematic 3’ UTR Shortening Associated with T Cell Activation and Cellular Proliferation
mRNA stability, localization and translation are largely determined by sequences in the 3’ untranslated region (UTR). Here, we describe a conserved program of increased expression of mRNAs derived from upstream polyadenylation sites (PAS) following activation of primary murine CD4+ T lymphocytes. This program, resulting in shorter 3’ UTRs, is a characteristic of immune cell activation and strongly correlates with proliferation across diverse cell types and tissues. Forced expression of full-length 3’ UTRs conferred differences in protein expression that could in some cases be eliminated by deletion of predicted microRNA target sites in the variably included region. Together, our data indicate that gene expression is coordinately regulated such that states of increased proliferation are associated with widespread reductions in the 3’ UTR-based regulatory capacity of mRNAs.
Timothy Nilsen, PhD
Mechanisms of MicroRNA-Mediated Gene Regulation in Animal Cells
Several lines of evidence suggest that microRNAs (miRNAs) regulate the expression of the majority of genes in animals. In almost all cases, miRNAs appear to function by binding to target mRNAs and repressing protein synthesis. The molecular mechanism(s) by which repression is achieved remains controversial and evidence for many seemingly contradictory modes of action have been proposed. In this presentation, the evidence for multiple mechanisms of miRNA function will be evaluated and discussed.
Mark A. Kay, MD, PhD
A functional Explanation for Restricting microRNA Targets to the Non-Coding Regions of mRNAs
11:30 am - 1:30 pm
11:45 am - 1:00 pm
Room 108
Speakers
Barrie J. Carter, PhD
Terence R. Flotte, MD
Career Development: Academic vs. Industry
11:45 am - 1:00 pm
Room 107
Speaker
Malcolm K. Brenner, MD, PhD
Gene Therapy and Cancer
1:30 pm - 2:45 pm
Room Ballroom A-C
Co-Chairs
Theodore Friedmann, MD
Donald B. Kohn, MD
Speakers
Karen S. Aboody, MD
Stem Cell-Mediated Cancer Therapy: A Tumor-Selective Gene Delivery Approach
Neural stem/progenitor cells (NSCs) display inherent tumor-tropic properties that can be exploited for targeted delivery and distribution of anti-cancer agents to invasive and metastatic tumors. When used as a delivery vehicle to localize therapeutic gene products directly to tumor sites, NSCs offer a way to reduce many limitations of currently available surgical, radiation and chemotherapeutic treatments. We postulate that this tumor-selective, NSC-mediated gene delivery approach, in combination with ongoing therapeutic approaches, can potentiate therapeutic indices to eradicate invasive and residual tumor cells, while minimizing toxicity to normal tissues. Significant therapeutic efficacy has been acheived with genetically modified stem cells in pre-clinical models of glioma, melanoma brain metastases, medulloblastoma, and disseminated neuroblastoma. Studies elucidating the factors and signaling pathways involved in this stem cell-tumor tropism, as well as investigations of NSC migration and tumor distribution patterns in real-time with Cellular Magnetic Resonance Imaging, will provide essential information for translation and optimization of this novel cancer treatment approach in clinical trials that are currently under development.
Maciej S. Lesniak, MD, FACS
Adenoviral Virotherapy for Malignant Brain Tumors
Malignant brain tumors represent an incurable form of primary brain cancer. Gene therapy has shown promising results in early clinical trials and new and novel approaches are needed to further advance the field. This presentation will address the development of novel adenoviral oncolytic vectors which contain transductional and transcriptional modifications that render them highly efficacious and specific for brain tumors. In addition, new and improved means of viral delivery to the brain will be discussed, with a special emphasis on neural and mesenchymal stem cells.
Dmitry M. Shayakhmetov, PhD
Adenovirus-Host Interplay and the Development of Efficient Vectors for Gene Therapy
The understanding of the basic aspects of virus interactions with host cells is of fundamental importance for understanding viral diseases. However, streamlined application of basic virology data to the development of viral vectors for gene therapy often leads to surprising and unpredictable outcomes. When virus particles are delivered in vivo via routes and at doses that are markedly different from those causing natural infection, an unforeseen array of host factors and cell types comes into play. These new host factors and cell types can modulate the viral vector infectivity and induce severe host responses that compromise the benefits of the proposed therapy. In this talk, we will describe recent findings on host factors and host responses that play critical roles in modulating adenovirus interactions with the host after intravenous vector delivery.
3:00 pm – 5:00 pm
(Abstracts 1-8)
Room 304
Co-Chairs
Brian K Kaspar, PhD
Selvarangan Ponnazhagan, PhD
3:00 pm – 5:00 pm
(Abstracts 9-16 and 808; Abstract 11 Withdrawn)
Room 210
Co-Chairs
Maria A. Croyle, RPh, PhD
Dmitry M. Shayakhmetov, PhD
3:00 pm – 5:00 pm
(Abstracts 17-24)
Room 100
Co-Chairs
James E. Hagstrom, PhD
Carol H. Miao, PhD
3:00 pm – 5:00 pm
(Abstracts 25-32)
Room 112
Co-Chairs
William Hauswirth, PhD
Jean Bennett, MD, PhD
3:00 pm – 5:00 pm
(Abstracts 33-40)
Room 311
Co-Chairs
Dale Ando, MD
Richard G Vile, PhD
3:00 pm – 5:00 pm
(Abstracts 41-48)
Room 309
Co-Chairs
William S. M. Wold, PhD
Konstantin G. Kousoulas, PhD
3:00 pm – 5:00 pm
(Abstracts 49-56)
Room 208
Co-Chairs
Amit Nathwani, MD, PhD
John T. Gray, PhD
3:00 pm – 5:00 pm
(Abstracts 57-64)
Room 312
Co-Chairs
David W. Emery, PhD
Derek Persons, MD, PhD
3:00 pm – 5:00 pm
(Abstracts 65-72)
Room 302
Co-Chairs
Peter A. Campochiaro, MD
Jeffrey A. Medin, PhD
3:00 pm – 5:00 pm
(Abstracts 73-80)
Room 207
Co-Chairs
Bruce Bunnell, PhD
To be announced
5:00 pm – 8:00 pm
Room Exhibit Hall A, Plaza Level
5:00 pm – 8:00 pm
Room Exhibit Hall B, Plaza Level
(Abstracts 81 through 99)
(Abstracts 100 through 111)
(Abstracts 112 through 130)
(Abstracts 131 through 146)
(Abstracts 147 through 163; Abstract 162 Withdrawn)
(Abstracts 164 through 184; Abstract 183 Withdrawn)
(Abstracts 185 through 194)
(Abstracts 195 through 214)
(Abstracts 215 through 228)
(Abstracts 229 through 246)
(Abstracts 247 through 263; Abstract 252 Withdrawn)
(Abstracts 264 through 277)
(Abstracts 278 through 295)
7:00 pm - 10:00 pm
Room 312
Co-Chairs
Pedro Lowenstein, MD, PhD
Maria Grazia Roncarolo, MD, PhD
Speakers
Pedro Lowenstein, MD, PhD
Maria Grazia Roncarolo, MD, PhD
Round Table Participants
Dwight Koeberl, MD, PhD & Ronald K. Scheule, PhD
Amit Nathwani, MD, PhD, Katherine A. High, MD & James M. Wilson, MD, PhD
Barrie J. Carter, PhD & Pervin Anklesaria, PhD
Pedro Lowenstein, MD, PhD & Michael Kaplitt, MD, PhD
Ignacio Anegon, MD & John Iacomini, PhD
Fulvio Mavilio, PhD & Soosan Ghazizadeh, PhD
Adrian J. Thrasher, MD, PhD & Maria Grazia Roncarolo, MD, PhD
Jeffrey Chamberlain, PhD
Hildegund CJ Ertl, MD
Christopher Walker, MD
Clinical gene therapy has made major advances over the last decade which has seen the treatment and even cures of both inherited diseases and cancer. Nevertheless, the immune system continues to challenge the therapeutic benefits of gene therapy. In some cases, adverse immune reactions have led to stopping clinical trials. In turn, this has stimulated a deeper understanding of the immune responses to gene therapy vectors, and the development of improved vectors and novel therapeutic approaches. This Open Forum will start with two very brief introductions to place the challenge posed by the immune system in the context of clinical gene therapy trials. This will be followed by an Open Discussion to be led by questions from the audience to the Round Table Participants, and moderated by the Co-Chairs! The Immunology Committee has thus invited a large group of gene therapy specialists representing a wide swath of expertise from basic immunology to clinical trials to address the audience’s questions. This Open Forum and Discussion follows in the footsteps of an earlier successful edition held two years ago and co-Chaired by Hildegund CJ Ertl and Pedro Lowenstein at the 8th Annual Meeting in St. Louis. Coffee and sweets will be provided, and audience participation is a must for this event! Please come prepared with your questions and challenges for the panel. This is your opportunity to have your immune challenges addressed by the experts.
7:00 pm - 10:00 pm
Room 304-306
Chair
Boro Dropulic, PhD
Speakers
Boro Dropulic, PhD
Protein and Vaccine Production
Jon Karpilow, PhD
Research Applications: Expression of RNAi with Lentiviral Vectors
Jeffrey A Medin, PhD
Lentiviral Vectors for treatment of GVHD
Stanton L. Gerson, MD
Lentiviral Vectors for Stem Cell Therapy Glioblasoma
Bruce L. Levine, PhD
Lentiviral Vectors for Leukemia therapy
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