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Presidential Symposium 300 8:00 AM - 10:15 AM Room: Ballroom AB Presidential Symposium
ChairR. Jude Samulski, PhD
Speakers
Kathy L. Hudson, PhD Catalyzing Innovation to Advance Translational Sciences The National Institutes of Health’s newest Center, the National Center for Advancing Translational Sciences (NCATS), aims to catalyze the generation of innovative methods and technologies that will enhance the development, testing and implementation of diagnostics and therapeutics. The Center is re-engineering the process of translating scientific discoveries into better patient care, with a focus on reducing, removing or bypassing bottlenecks in the research pipeline. This presentation will include an overview of new NCATS programs and models for collaboration in translational research.
Karl Deisseroth, MD, PhD Optogenetics: Development and Application In this lecture, new tools for optogenetics will be discussed and practical techniques for application both in basic science and in disease models will be covered. We will cover new genomically identified opsins as well as engineered chimeric and mutated opsins. New transgenic animals and viral tools will also be reviewed, as well as approaches for targeting light and opsin expression to circuit elements of interest, and methods for applying optogenetics both in normally-functioning neural systems and in models of neurological and psychiatric disease.
Exhibit Hall Coffee Social 10:15 AM - 11:00 AM Room: Hall A
Scientific Symposium 310 11:00 AM - 1:00 PM Room: 202 AB Advances in Non-Viral Gene Transfer and Targeting
Co-ChairsRichard Heller, PhD Amir S. Khan, PhD
Mitsuo Oshimura, PhD Human Artificial Chromosome for the Non-Integrated Stable Gene Expression Gene therapy has been envisioned to provide a direct and permanent correction of genetic defects. To achieve the desired effects, therapeutic genes need to be carried by safe and effective vectors that can deliver foreign genes to specific cells and thereafter sustain their expression in a physiologically regulated fashion. Human artificial chromosome is exogenous, non-integrated mini-chromosome. Several experimental data showed that HAC would be advantageous over current gene delivery methods in several points. Thus, a combination of stem cell-based tissue engineering and HAC technology may open up new avenues for gene-and cell-therapies.
Michael SD Kormann, PhD In Vivo Delivery of Chemically Modified mRNA Chemically modified mRNA has recently shown promise as an alternative to traditional gene therapy approaches. We have demonstrated the successful in vivo application of modified mRNA in both a rare and high prevalence disease model. First, mRNA encoding for Surfactant Protein B (SP-B) showed life-saving efficacy in a murine model of SP-B deficiency. Secondly, modified Foxp3 mRNA was able to rebalance T helper cell responses and protect against airway hyperresponsiveness, tissue inflammation and goblet cell metaplasia in a murine model of Th2-driven allergic asthma. These studies suggest that chemically modified mRNA is a promising therapeutic tool for the treatment of lung disease, where intermittent bursts of gene expression or repeated dosing are favored.
Claire Evans, PhD Electroporation-mediated DNA Delivery: Clinical Trial Update DNA vaccines have many appealing characteristics, including the ability to induce both cellular and humoral immune responses, ease of manufacturing, flexible design, and lack of anti-vector responses that can limit antigen-specific responses. Although conventional injection of DNA vaccines can induce robust responses in small animal models, in human clinical trials conventional delivery has resulted in weak and inconsistent immune responses. Delivery of DNA vaccines with electroporation (EP) greatly enhances antibody and T cell responses in multiple animal species. Encouragingly, initial human clinical trial results indicate that more potent immune responses are induced with EP delivery compared to conventional delivery. An overview of clinical trials using EP to deliver DNA vaccines will be presented, as well as some promising immune response data.
Shondra Miller, PhD High-frequency Genome Editing Using ssDNA Oligonucleotides with Zinc Finger Nucleases Genome engineering using Zinc-Finger Nucleases (ZFNs) has enabled researchers to make precise and efficient modifications to multiple different cell lines and organisms. ZFNs are engineered proteins that create targeted double strand DNA breaks, and the repair of these breaks by endogenous cellular repair machinery can lead to gene knockout, gene knockin, and other user-defined genomic modifications. Traditionally, user-specified modifications are made by co-delivery of the ZFN encoding reagents and a repair substrate in the form of a donor plasmid that contains the desired change as well as homology arms. We will present methods using ssDNA oligonucleotides as repair substrates after ZFN-induced double strand break. In this work we have used these simple ssDNA oligo donors to achieve three distinct outcomes: (1) targeted point mutations, (2) targeted genomic deletions from 100bp to 100kb and (3) concomitant targeted insertion and genomic deletion.
Scientific Symposium 311 11:00 AM - 1:00 PM Room: 204 C Advances in the Design and Application of DNA Cancer Vaccines
ChairSattva S. Neelapu, MD
Sattva S. Neelapu, MD DNA Vaccines for Lymphoid Malignancies A recently completed randomized controlled double-blind phase III trial showed that administration of idiotype (Id) protein vaccine prolongs disease-free survival in patients with follicular lymphoma providing proof of principle that therapeutic cancer vaccination can improve clinical outcome. DNA Id vaccines are an alternative to protein vaccines because of their ease of generation. However, DNA vaccines have limited efficacy when used alone. Novel strategies to enhance the efficacy of DNA vaccines will be reviewed.
Don J. Diamond, PhD Salmonella Delivery of RNA Therapeutics Redefines its Role as a Cancer Therapy Salmonella Typhimurium has been known for over fifty years to colonize human tumors, but its extreme virulence without attenuation minimized its role as a cancer therapeutic. Later developments resulted in attenuated strains that were safe to administer to humans, but the extreme attenuation reduced their value in the clinic. Disappointing results in several clinical trials led to the current state of Salmonella as a failed therapy. We have attempted to reinvent the field of Salmonella therapy by engineering a well-known attenuated strain called VNP20009 with plasmids encoding small hairpin RNA (shRNA) targeting the immunosuppressive shield of tumors that contributes to failure of many immunotherapy approaches. We report on initiatives targeting two significant players in the immunosuppression field: indoleamine 2,3-dioxygenase and arginase 1. Employing systemic delivery of Salmonella incorporating plasmids expressing shRNA for either molecule enables significant increase in therapeutic index such that superior antitumor properties caused durable regression of highly malignant murine transplantable solid tumors and human or murine melanomas. We will present data that supports immunologic mechanisms of action of Salmonella therapeutics that only occur when shRNA molecules are expressed. By reinvigorating the search for a superior approach to Salmonella therapy, its role as a cancer therapeutic should be given another look.
Rose Ann Padua, PhD DNA Vaccines in Combination with All-Trans Retinoic Acid Induces Immune Responses and Extends Life-Span in a Mouse Model of Acute Promyelocytic Leukemia DNA vaccination with all-trans retinoic acid (ATRA) induces long term remissions with immune responses in a mouse model of acute promyelocytic leukemia (APL) (Padua et al.2003, Nat. Med. 9:1413-7; Furugaki et al. 2010, Blood, 15:653-6). This combination of an immunomodulator and inducer of apoptosis with DNA vaccination was used with two DNA constructs; a specific PML-RARa sequence with tetanus toxin FrC as an adjuvant and a novel adjuvant construct comprising novel sequences designated as Flipper, containing additional GC-rich sequences and coding for unique peptides. Extended survival was observed with immune responses measured with both vaccines. We hypothesize that both constructs are acting as adjuvants to increase pre-existing immune responses initiated by the tumor antigens released upon induction of apoptosis by ATRA (Robin et al. 2006, Blood 108:1972-4). This adjuvant strategy should theoretically be effective against a wide variety of different tumor antigens in a wide variety of different malignancies.
James L. Gulley, MD, PhD Safety and Preliminary Evidence of Efficacy of Combining a Therapeutic Cancer Vaccine (PSA-TRICOM) with an Immune Checkpoint Inhibitor (ipilimumab) Prostvac is an experimental vaccine in phase III testing in Prostate cancer. A randomized phase II study suggested a 44% reduction in death rate for patients taking vaccine. In an attempt to improve on the clinical activity of this vaccine we completed a phase I safety study of the combination of Prostvac with ipilimumab, an immune checkpoint inhibitor which was recently FDA approved. This 30 patient trial demonstrated the safety and activity of the combination and opens the door for other combination studies of vaccine with immune checkpoint inhibitors.
Scientific Symposium 312 11:00 AM - 1:00 PM Room: 201 AB Clinical Trials II
ChairBarry J. Byrne, MD, PhD
Terence R. Flotte, MD Persistence of Transgene Expression for 1Year in a Phase 2 Trial of Intramuscular Administration of rAAV-AAT Nine alpha-1antitrypsin (AAT) deficient adults were injected with a rAAV1-AAT vector at doses ranging from 6.0x10e11 to 6.0x10e12 vg/kg in a phase 2 clinical trial. In an earlier report of this trial, we demonstrated persistence of wild-type(M) AAT expression in the serum and in the injected muscle at 90 days post-injection, despite the presence of capsid-specific T-cell responses and local cellular infiltration. In this report, we extend those findings to 1 year and observe continued expression of M-AAT in the serum at levels at or above those seen at 90 days, without any apparent vector-related adverse events. These data support continuing the dose escalator in future studies of rAAV1-AAT delivery to muscle.
David H. Kirn, MD Clinical Proof-of-Concept with JX-594, a Cancer-Targeted and Transgene-Armed Oncolytic Vaccine Virus Cancer gene therapy and oncolytic virus agents have not achieved product marketing approvals despite over two decades of R and D and excellent safety profiles. Hurdles to efficacy have been identified and include 1) delivery to a sufficient fraction of cancer cells within a tumor mass, 2) reliance on a single MOA, and 3) insufficient IV delivery to metastatic tumors systemically. We proposed that targeted and transgene-armed oncolytic vaccinia virus products could overcome all three of these hurdles. JX-594 is the lead product in this emerging therapeutic class (SOLVE: selective oncolytic vaccinia engineering), with over 125 patients treated to date in multiple clinical trials (Phase 1, 2 and 2b). Clinical proof-of-concept data will be presented, including evidence for multiple MOA, anti-tumor activity and survival prolongation in patients with advanced solid cancers.
Carl H. June, MD Classic CARS, Muscle CARS and Sports CARS for Cancer The recent clinical success of T cells redirected with chimeric antigen receptors (CARs) at several academic centers indicate this strategy as the new frontier for the immunotherapy of hematological malignancies. A number of issues facing the field will be addressed such as extending CAR T cell therapy beyond B cell malignancies, and whether CAR T cells may have a role in solid tumor therapy. Finally, approaches to control the fate of CAR T cells will be addressed.
Barry J. Byrne, MD, PhD Clinical Studies of Gene Therapy for Ventilatory Failure in Neuromuscular Disease Gene therapy in inherited muscle diseases has traditionally been focused on improved ambulation or arm function. In the management of Pompe disease, cardiopulmonary failure is the most severe manifestation leading to mortality in the first year of life. Therefore, we have conducted a phase I/II study in children 2-18 years of age who require ventilatory assistance following initial treatment with enzyme replacement therapy. The findings from this study support the safety of AAV vectors for this indication and demonstrate that gene transfer to muscle and the phrenic motor system can improve ventilatory function.
Scientific Symposium 313 11:00 AM - 1:00 PM Room: 203 AB Personalized Medicine: From Infancy to Alzheimer's
ChairNelson A. Wivel, MD
Theodore Friedmann, MD Genetic Enhancement: Can We and Should We? The development of efficient and safe methods for human gene transfer and their successful application to gene therapy suggest that similar methods may be applied to gene-based enhancement of normal human traits. With continued success in gene therapy, opportunities will arise for improving quality of life in addition to treating disease. For instance, promising advances toward gene therapy of muscular dystrophies and disease-related muscle atrophy provide impetus for preventing or reversing the diminishing muscle function of "normal" age-related muscle loss (sarcopenia) and even for enhancing muscle function in Sport. It is not too early to prepare ethically for such possible applications, especially in light of the broad societal acceptance of pharmacological and surgical enhancements and of the explosive development of genetic technologies that will make gene-based enhancement possible.
Arthur Caplan, PhD Given its Past, What Moral Challenges Lie Ahead for Gene Therapy? The death of Jesse Gelsinger and adverse events in other subjects in gene therapy trials created a very difficult ethical climate for gene therapy. However, further work on vectors, careful studies utilizing animals and the promising efficacy of various forms of gene therapy in treating or ameliorating immunodeficiency disorders, bone marrow cancer, one form of inherited blindness (LCA, a form of hemophilia (Hemophilia-B) and chronic lymphocytic leukemia have rightly renewed interest in pushing gene therapy forward as a treatment modality. What ethical challenges must be addressed for progress to continue both in working with subjects, their families, advocacy organizations, regulators, investors and the media?
Erica C. Jonlin, PhD Challenging Ethical Issues Associated with IRB Review of Personalized Medicine The use of high-throughput molecular tools such as whole genome/exome sequencing, RNA sequencing, and other state-of-the-art technologies allow analyses of an individual patient’s tumor that have previously been impossible. Results from such molecular tests potentially enable a personalized and targetted approach to cancer treatment. However, because many of these molecular approaches, as well as the treatments the results may suggest, are investigational, the use of the “personalized medicine approach” is subject to IRB review. Human subjects protection regulations were designed to protect and therefore address the health, safety, rights, and welfare of individuals enrolled in clinical trials, in which there is a single protocol, set procedures, and only one or a few investigational agents under study. This presentation will discuss the application of IRB regulations to a personalized medicine protocol, and the challenging ethical issues associated with IRB review of personalized medicine.
Scientific Symposium 314 11:00 AM - 1:00 PM Room: 204 AB Safety Switches and Suicide Genes for Cell Therapy
Co-ChairsGianpietro Dotti, MD Karin M.L. Gaensler, MD
Chiara Bonini, MD Clinical Use of Suicide Genes in Cancer Immunotherapy Suicide gene therapy applied to allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been one of the first clinical applications of gene therapy. In allo-HSCT the antileukemic potential mediated by alloreactive lymphocytes towards patient-specific antigens, such as minor and major histocompatibility antigens, is counterbalanced by the Graft-versus-Host-Disease (GvHD), an immune-mediated complication due to the recognition of healthy tissues by donor lymphocytes. The risk of GvHD increases with the level of HLA disparity between host and donor, and leads to impaired quality of life and reduced survival expectancy, particularly in patients transplanted from HLA-mismatched donors. Suicide gene therapy has been proposed to modulate alloreactivity. The prototype and first suicide gene tested is HSV-tk. This suicide gene/prodrug system requires cell cycle for optimal killing. In the context of allo-HSCT, this characteristic ensures a further level of specificity in GvHD control, by allowing to selectively kill highly proliferating alloreactive cells during GvHD, while sparing resting T cells. 128 patients have been treated in 10 phase I-II clinical trials worldwide with donor lymphocytes expressing the HSV-tk suicide gene, with the purpose of enforcing the graft-versus-tumor (GvT) effect and/or promoting a functional post-transplant immune reconstitution (graft-versus-infection-GvI) while allowing control of GvHD. This approach proved highly feasible, safe and effective in promoting a dynamic and patient-specific modulation of alloreactivity. TK cells engrafted in the majority of patients and a clinical benefit, measured as improvement of hematopoietic chimerism, malignant regression and/or immune reconstitution, was reported for 65 patients (51%). GvHD grade II-IV was observed in 28 patients (22%) and was always rapidly and completely controlled by the activation of suicide machinery. Being of viral origin HSV-TK is immunogenic in humans. Immunity against the transgene was reported in 14 out of 87 patients who received TK cells after an HLA-identical allo-SCT. The quality of immune reconstitution at the time of TK-cell administration was the most predictive variable. On the contrary, no immunity against HSV-TK was ever detected in the 41 patients who received TK cells after transplantation of haploidentical CD34-selected cells, indicating that the infusion of TK cells to highly immunosuppressed patients is not limited by the development of transgene-specific immune responses. Circulating TK cells were detected long-term (for more than 14 years). No adverse event correlated to the gene transfer procedure was ever reported. Long-term assessment in a subset of the reported studies included the clinical and molecular monitoring of 20 patients with more than 5 years follow-up, and further confirmed the overall high benefit/risk ratio of the TK-cell approach in allogeneic hematopoietic stem cell transplantation. A phase III multicentric, randomized clinical trial sponsored by Molmed, is currently undergoing in the context of haploidentical HSCT.
David M. Spencer, PhD CaspaCIDe Provides an Efficient, Non-Immunogenic, Low Basal Activity Safety Switch Solution for Cell Therapy An efficient method to rapidly eliminate obsolete or deleterious cells in vivo is an important pre-requisite for enabling the full actualization of cellular therapy applications. First generation suicide genes were based on xenogeneic, and hence immunogenic, enzymes that converted a mildly toxic pro-drug to a highly toxic compound. In contrast, inducible iCapase9 (CaspaCIDe) relies on chemically induced dimerization of a re-engineered, human Caspase9 gene to rapidly trigger apoptosis in iCaspase9-expressing cells following administration of the bioinert, synthetic molecule, AP1903. The development of this unique reagent along with clinical results will be presented.
Luigi M. Naldini, MD, PhD Micro - RNA Based Regulation of Transgene Expression
Eirini P. Papapetrou, MD, PhD A miRNA-regulated Suicide Switch for Safer iPS Cells Human pluripotent stem cells offer great promise for cell therapies. However, a major concern - inherent to their pluripotent nature - is the risk of teratoma formation. To confer protection against teratoma-initiating pluripotent cells that may contaminate a differentiated cell graft, we engineered an HSV-tk suicide gene regulated by let7 miRNAs (tk-let7), a miRNA family widely expressed in all differentiated cell types but not in undifferentiated stem cells. We show that beta-thalassemia patient undifferentiated iPSCs expressing tk-let7 are sensitive to killing by ganciclovir (GCV), whereas their differentiated progeny are protected. GCV treatment in vivo inhibits teratoma growth. To confer safer, reliable and unsilenced expression, we used recombinase-mediated cassette exchange (RMCE) to target the tk-let7 transgene into a genomic safe harbor site in transgene-free iPSCs.
Scientific Symposium 315 11:00 AM - 1:00 PM Room: 201 C Vaccine Frontiers
ChairPhilip R. Johnson, MD
Andrea Amalfitano, DO, PhD Advancing Vaccines with Use of Adenovirus Based Gene Transfer Vectors In this session, the many benefits as to the use of first generation, as well as advanced generation, Adenovirus based gene transfer vectors will be broadly summarized, inclusive of examples as to their ease of scale up for cGMP deployment to thousands of patients, the over decades worth of confirmed safety in thousands of humans, participating in hundreds of clincial trials, as well the several intrinsic biological attributes that enhance the utility of Adenovirus vectors as vaccine platforms in general. More specifically, the interactions of Adenoviruses with several arms of the innate immune system will be reviewed in the context of highlighting how these interactions facilitate and promote beneficial inductions of antigen specific adaptive immune responses to Adenovirus vaccine expressed antigens. Additionally, Adenovirus vector modifications that mitigate or minimize limitations of these vectors for vaccine use, such as in the context of pre-existing Adenovirus immunity, will also be commented upon, with updates on the use of advanced generation, [E1-,E2b-] Adenovirus based colon cancer targeting vacc ines in ongoing Phase II human clinical trials. Finally, several targeted enhancemnts designed to improve the ability of Adenovirus vaccines to beneficially interact with the innate immune system will also be highlighted as an example of how this diverse vaccine platform may be deployed for use against difficult, vaccine amenable clinical diseases.
Maria P. Limberis, PhD AAV-mediated Expression of Neutralizing Antibody in Airway: An Innovative Approach for Pandemic Influenza In the USA influenza is the seventh leading cause of death with children, elderly and pregnant women most at risk. In 2009, the H1N1 pandemic strain resulted in more than 18,000 deaths worldwide. We will present the development of a passive vaccine based on adeno-associated virus (AAV) vector for the prevention and control of the spread of influenza. This AAV-based vaccine is administered non-invasively via the nose to express broadly-neutralizing antibody across the nasal and lung mucosa and provides protection against a lethal challenge with influenza.
Linda B. Couto, PhD Novel Strategy for Treatment of HCV Infection by AAV-Mediated RNA Interference Hepatitis C virus (HCV) infection remains a major global health care problem, as approximately 3% of the world population, or 170 million people, are chronically infected with this virus. Development of treatments and vaccines against HCV are challenging because of its broad genetic diversity and its propensity to mutate. The successful treatment of HCV will most likely require a combination of multiple drugs to prevent the generation of viral escape mutants, and RNA interference (RNAi) provides a means for achieving this. We are exploiting the endogenous miRNA-17-92 cluster as a scaffold for the expression of multiple exogenous miRNAs that are complementary to the HCV genome. The miRNAs are delivered to cells using recombinant AAV vectors (rAAV-Cluster 5) and are expressed in hepatocytes, the site of HCV replication. Using AAV-mediated gene delivery, this artificial anti-HCV miRNA cluster inhibited bona fide HCV replication by 98% in Huh7.5 cells. Furthermore, when HCV was serially propagated on rAAV-Cluster 5-transduced cells, it was completely eliminated (> five log decrease) from the culture within four rounds of propagation. This is in contrast to AAV vectors that expressed just a single miRNA, which inhibited HCV replication by two logs, but was incapable of eradicating the infection. Following a single injection of mice with rAAV-Cluster 5, efficient gene transfer was observed, and all five miRNAs were expressed, which resulted in up to 98% gene silencing of reporter plasmids. No liver toxicity, as a result of miRNA expression, was observed in mice followed for up to 6 months post-injection, unlike what has been seen using AAV vectors expressing short hairpin RNAs. These data strongly suggest that rAAV-Cluster 5 will be highly effective against an HCV infection in human hepatocytes, which harbor lower copy numbers of HCV than Huh7.5 cells, and where the AAV vector is predicted to be stably maintained. Thus, this vector represents a novel alternative strategy for the treatment of HCV infection.
Maria A. Croyle, RPh, PhD Modeling Pre-Existing Immunity to Adenovirus: Lessons Learned Through the Development of a Filovirus Vaccine Prior exposure to common environmental viruses has been a significant incertitude for routine use of certain recombinant viruses such as adenovirus and human parainfluenza virus in gene transfer and immunization platforms. Although a significant effort has been put forth to develop methods to achieve significant therapeutic responses in those with this particular immunological state, progress has been moderate. Mucosal administration of recombinant viruses, the first simple and straightforward approach to address this issue, did foster significant transgene expression in those with pre-existing immunity (PEI), however, this was limited by the manner in which prior contact was established. This and results from the clinic suggest that this particular immunological state is poorly characterized and not well understood. The impact of PEI on the T and B cell mediated immune response to a secreted immunogen (Ebola Zaire glycoprotein) after immunization by different routes (intramuscular (IM), intranasal (IN) and sublingual (SL)) and how the manner by which PEI is established also influences these responses will be discussed. Examples of how, once the basic immunological patterns are known, addition of certain excipients to a preparation can improve specific arms of the immune response in those with prior exposure to a vaccine vector will also be presented.
Lunch Break (On Own - Not Provided) 1:00 PM - 2:15 PM
Oral Abstract Session 320 2:15 PM - 4:15 PM Room: 201 C Adenovirus Vectors: Immunity and Systemic Delivery
Co-ChairsVincenzo Cerullo, PhD Victor W. Van Beusechem, PhD
Oral Abstract Session 321 2:15 PM - 4:15 PM Room: 201 AB Nuclease Mediated Gene Targeting
Co-ChairsMatthew H. Porteus, MD, PhD R. Scott McIvor, PhD
Oral Abstract Session 322 2:15 PM - 4:15 PM Room: 204 AB Gene and Cell Therapy for Genetic and Metabolic Disorders: Focus on Storage Disorders
Co-ChairsCharles P. Venditti, MD, PhD Andy Wilber, PhD
Oral Abstract Session 323 2:15 PM - 4:15 PM Room: 202 AB Infectious Diseases and Vaccines
Co-ChairsPhilip R. Johnson, MD John A. Zaia, MD
Oral Abstract Session 324 2:15 PM - 4:15 PM Room: 204 C Cancer - Immunotherapy: Harnessing Gene Therapy to Improve Anti-tumor Effect
Co-ChairsAkseli Hemminki, MD, PhD Richard G. Vile, PhD
Oral Abstract Session 325 2:15 PM - 4:15 PM Room: 203 AB Oligonucleotide & RNAi Therapeutics
Co-ChairsJoel R. Chamberlain, PhD Paloma H. Giangrande, PhD
Oral Abstract Session 326 2:15 PM - 4:15 PM Room: Ballroom AB Late Abstract Session
Co-ChairsAnton P. McCaffrey, PhD Matthew D. Weitzman, PhD
Exhibit Hall Open: Networking Reception & Poster Session II 4:15 PM - 6:15 PM Room: Hall A
Partnered Program 330 6:30 PM - 8:30 PM Room: 201 AB Global Gene and Cell Therapy Summit and Reception
Supported by the Kanghong Pharmaceutical Group, Co., Ltd. Jointly planned by the European Society of Gene & Cell Therapy and the Japan Society of Gene Therapy
ChairMalcolm K. Brenner, MD, PhD
Yu-Quan Wei, MD, PhD Progress in Gene and Cell Therapy in China The presentation will briefly review the progress in the gene and cell therapy in China. The gene and cell therapy in China are still supported by the government funding. The researchers in about 50 core teams from public or private sectors in China are engaged in the gene and cell therapy, including stem cell therapy. Recently, the researchers pay a special attention to the new strategy for the development the novel vectors for gene therapy.
Kenzaburo Tani, MD, PhD Current Status of Clinical Gene Therapy in Japan In Japan, 38 clinical gene therapy protocols have been submitted and reviewed since 1995, and 26 of them target malignancies. Cancer gene therapy in Japan includes gene therapies using cDNAs of GM-CSF, p53, MDR1, HSV-tk, IFN-beta, IL-12gene, T cell receptor, REIC and NK4. Recently, oncolytic virotherapy has been extensively investigated clinically and preclinically in Japan.
Yasufumi Kaneda, MD, PhD Cancer Virotherapy Using Non-replicating Sendai Virus Particle (HVJ envelope) We developed a novel DDS using non-replicating Sendai virus particle (HVJ envelope). We discovered multiple anti-tumor activities of HVJ envelope itself. Clinical studies to test the safety and efficacy of HVJ envelope in cancer patients have started in Japan.
Hiroaki Mizukami, MD, PhD Hemophilia Gene Therapy We have been working on single stranded AAV8-mediated hemophilia gene therapy using monkeys. Notably, we have developed sensitive NAb assay in order to detect low titer serum samples. As a natural extension, we are preparing clinical trials utilizing these results.
Alessandra Biffi, MD HSC Gene Therapy Trial in Metachromatic Leukodystrophy
Amit Nathwani, MD, PhD Stable Therapeutic Expression of Transgenic FIX Following AAV Mediated Gene Transfer in Patients with Severe Haemophilia B
Katherine A. High, MD Progress in Gene and Cell Therapy in the US: 2011-2012
