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SELECTBIO Conferences Cell & Gene Therapy Asia 2019

Cell & Gene Therapy Asia 2019 Agenda

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Monday, 11 November 2019


Preclinical Transplantation Study of iPS Cell-Derived Cardiomyocytes in Non-Human Primate
Yuji Shiba, Professor, Department of Regenerative Science and Medicine, Shinshu University, Japan

Induced pluripotent stem cells (iPSCs) have promising potential as a source of autologous patient-specific cardiomyocytes for cardiac repair, obviously providing a major benefit in terms of immune rejection. However, autologous transplantation comes with substantial challenges related to manufacturing and regulation. Although major histocompatibility complex (MHC)-matched allogeneic transplantation is a promising alternative strategy, surprisingly few immunological studies have been carried out with iPSCs. Here, we established an allogeneic transplantation model using cynomolgus monkey, whose MHC structure is identical to that of humans. iPSCs were generated from fibroblasts from an animal with a homozygous MHC haplotype (HT4), and the cells were differentiated into cardiomyocytes (iPSC-CMs). Five HT4 heterozygous monkeys were subjected to myocardial infarction followed by direct intramyocardial injection of the iPSC-CMs. The grafted cardiomyocytes survived for 12 weeks with no evidence of immune rejection under treatment of clinically relevant doses of methylprednisolone and tacrolimus, and they showed indisputable electrical integration with host cardiomyocytes as assessed by use of our novel fluorescent calcium indicator, G-CaMP7.09. In addition, transplantation of the iPSC-CMs improved cardiac contractile function at 4 and 12 weeks post transplantation; however, the incidence of ventricular tachycardia was transiently but significantly increased when compared to the vehicle-treated control. MHC-matched allogeneic transplantation of iPSC-CMs regenerates infarcted non-human primate heart. Further research to control post-transplant arrhythmias is warranted.


Norio NakatsujiConference Chair

Title to be Confirmed.
Norio Nakatsuji, Chief Advisor, Stem Cell & Device Laboratory, Inc. (SCAD); Professor Emeritus, Kyoto University, Japan


Terry RissKeynote Presentation

Title to be Confirmed.
Terry Riss, Global Strategic Marketing Manager Cell Health, Promega Corporation, United States of America


AlleviTitle to be Confirmed.
Ricky Solorzano, CEO, Allevi


Multidisciplinary Oncolytic Virotherapy for Gastrointestinal Cancer
Toshiyoshi Fujiwara, Professor & Chairman, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan

Telomelysin (OBP-301) is an attenuated oncolytic adenovirus, in which the telomerase promoter drives expression of E1 genes. Telomelysin causes selective replication and lysis of a variety of human cancer cells, and also inhibits the repair of radiation-induced DNA double-strand breaks, leading to radiosensitization. A phase I study has confirmed the safety and biological activity of Telomelysin alone in patients with advanced solid tumors in the US. To further determine the feasibility, efficacy, and pharmacokinetics of Telomelysin in combination with radiotherapy, an investigator-driven clinical study was designed. Patients with histologically confirmed esophageal cancer who were not eligible for surgery or chemotherapy were enrolled into this study. Study treatment consisted of intratumoral needle injections of Telomelysin on days 1, 18, and 32 of treatment. Radiation therapy was administered concurrently over 6 weeks, beginning on day 4, to a total of up to 60 Gy. Virus administration was performed by intratumoral injection of the primary tumor through a flexible endoscope. Patients receive escalating doses of Telomelysin (1010 to 1012 virus particles [vp]). Seven, three, and three patients were enrolled and treated in the cohorts with 1010, 1011, and 1012 vp of Telomelysin, respectively. The patients comprised 10 males and 3 females, with median age of 79.7 years (range, 53 to 92 years). Common grade 1 and 2 toxicities included fever, esophagitis, pneumonitis, anorexia, constipation, and gastroesophageal reflux disease. All patients developed a transient, self-limited lymphopenia. Objective responses were complete response (CR) in 4, 2, and 2 patients in cohort 1, 2, and 3, respectively; all of them exhibited pathologically no viable malignant cells in biopsy specimens. Histopathologic examination in post-treatment specimens showed massive infiltration of CD8+ cells in 3 partially responded tumors. Multiple courses of endoscopic Telomelysin injection with radiotherapy were feasible and well tolerated in patients with esophageal cancer, and appeared to provide clinical benefit.


Current Status and Future Directions of CAR-T Cell Therapy
Keiya Ozawa, Professor Emeritus and Visiting Professor of the Division of Immuno-Gene & Cell Therapy, Jichi Medical University, Japan


Shoji TakeuchiKeynote Presentation

Title to be Confirmed.
Shoji Takeuchi, Professor, Center For International Research on Integrative Biomedical Systems (CIBiS), Institute of Industrial Science, The University of Tokyo, Japan


First Commercial Available Gene Therapy Drug “Collategen” in Cardiovascular Disease
Ryuichi Morishita, Professor of Clinical Gene Therapy, Osaka University School of Medicine, Japan

Gene therapy has emerged as a novel therapy to promote angiogenesis in patients with critical limb ischemia (CLI) caused by peripheral artery disease. We have focused on hepatocyte growth factor (HGF) as pro-angiogenic factors. In the clinical trials of phase III, the naked plasmid DNA encoding HGF showed the safety and their potential for symptomatic improvement in CLI patients. Improvement rate was 70.4 % in HGF and 30.8% in placebo in Fontaine III patients (P=0.014). HGF gene therapy achieved a significantly higher improvement rate of ischemic ulcers compared with placebo (100% vs. 40%, P=0.018). No major safety problems were observed. Based on phase III data, in this year, HGF will be launched in Japan market as the first gene therapy drug.


Kinichi NakashimaKeynote Presentation

Artificial Production of New Neurons in the Adult Central Nervous System
Kinichi Nakashima, Professor, Department of Stem Cell Biology and Medicine, Kyushu University, Japan

The body’s capacity to restore damaged neural networks in the injured central nervous system (CNS) is severely limited. Therefore, usefulness of neural stem cell (NSC) transplantation to replenish neurons has been extensively investigated, but because of gliogenic environment in the lesion site, effective neuronal production has not been satisfactorily successful. We have previously found that anti-epileptic drug valproic acid, also known as a histone deacetylase inhibitor, induced neuronal differentiation of NSCs, and reported that combinatorial treatment with VPA and NSC transplantation can supply newly generated neurons in injured spinal cord, leading to dramatic functional recovery after spinal cord injury (SCI). In the subsequent study, we have also shown that human iPSC-derived NSC, which are epigenetically restricted not to differentiate into glial cells, efficiently give rise to neurons in the injured spinal cord, inducing recovery of locomotor functions of mice after SCI. Although it is now understood that supply of new neurons has beneficial effects on the functional recovery, there still remain critical problems, such as tumorigenicity and time-consuming preparation of cells if we utilize iPSC-derived cells. As an alternative strategy to replenish new neurons in vivo, direct conversion from endogenous cells in non-neuronal lineages attracts much attention these days. We have recently found that microglia, which converge at lesion site after injury, can be converted to functional neurons both in vitro and in vivo by the expression of a single proneural transcription factor NeuroD1 (ND1). We also verified the molecular mechanisms of how ND1 provokes and suppresses neuronal and microglial programs, respectively. In this talk, I would like to introduce these our achievement and discuss future directions regarding treatments of CNS injuries.


Clinical Application of iPS Cell Therapy For Parkinson’s Disease
Asuka Morizane, Assistant Professor, Center for iPS Cell Research and Application (CiRA), Kyoto University, Japan

The innovation of induced pluripotent stem cells (iPSCs) and previous embryonic stem cell (ESC) technologies are drawing attention to their application for regenerative medicine. Parkinson’s disease (PD) is one of the most promising target diseases based on the history of fetal nigral transplantation in clinics. The technology of iPSCs offers a limitless and more advantageous donor source than aborted tissue. One of the advantages is possibility of preparing immunologically compatible donor cells from self-derived or allogeneic iPSCs. We have successfully established a protocol for donor induction with clinically compatible grade and have transplanted these neurons into PD models of mice, rats, and cynomolgus monkeys as preclinical studies. Based on these research results, the clinical trial of cell therapy for PD with iPS cells started since 2018. The presentation will include the recent research results and the proceedings of the clinical trial.


Gene Therapy For Neurological Diseases
Shin-ichi Muramatsu , Professor of Neurology, Jichi Medical University (JMU), Japan

Adeno-associated virus (AAV) vectors have been widely used for gene therapy. In Clinical studies on advanced Parkinson’s disease, investigators, including us, have shown the motor symptoms to be ameliorated along with an increased dopaminergic activity on positron emission tomography after gene transfer of aromatic L-amino acid decarboxylase (AADC) into the putamen. The beneficial effects of AADC gene transfer have also been shown in children with AADC deficiency. AAV vectors can achieve global transduction of the central nervous system by intravenous or intrathecal injection. We have been developing gene therapy for various diseases including sporadic amyotrophic lateral sclerosis, spinocerebellar ataxia 1, glucose transporter 1 deficiency, and GM2 gangliosidosis.


Chae-Ok YunKeynote Presentation

Optimizing the Delivery of Anticancer Immune Response-Inducing Oncolytic Adenovirus and Adjuvant Immunotherapeutic
Chae-Ok Yun, Professor, Department of Bioengineering, Hanyang University, Korea South

Currently, intratumoral injection of an oncolytic adenovirus (Ad) remains the conventional administration route in clinical trials. Nonetheless, the locally administered Ad disseminates to the surrounding nontarget tissues and has short biological activity due to immunogenicity of Ad, which inadvertently promotes rapid clearance and insufficient intratumoral retainment of therapeutics. To this end, we developed biocompatible and biodegradable hydrogels to enhance the therapeutic efficacy of oncolytic Ads via single intratumoral administration. A hydrogel-based intratumoral delivery of oncolytic Ads led to prolonged viral retainment within tumor tissues and restricted nonspecific shedding to normal tissues (up to 161.4-fold higher retainment than naked oncolytic Ad). Notably, hydrogel systems attenuated oncolytic Ad-mediated antiviral immune response, which can cause adverse inflammatory response, while preserving the viruses’ ability to induce robust antitumor immune response. One of the hydrogel was capable of efficiently co-delivering and protecting both therapeutic dendritic cells and oncolytic Ad in tumor tissues, thus potentiating the robust antitumor immune response by combination therapy regimen. Collectively, hydrogel-based delivery system enables biological activity of both immunotherapeutic agents could be preserved over a considerable time period in immunosuppressive and hostile tumor microenvironment that significantly diminishes the efficacy of immunotherapeutics. A delivery system, which simultaneously modulates both antiviral and antitumor immune response in a favorable manner to the potency and safety of oncolytic virotherapy in a complex immunological microenvironment of tumors, is of great importance as it may finally enable oncolytic virotherapy to reach its full potential and achieve optimal therapeutic outcome against clinical cancer.

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Add to Calendar ▼2019-11-11 00:00:002019-11-12 00:00:00Europe/LondonCell and Gene Therapy Asia 2019Cell and Gene Therapy Asia 2019 in Kobe, JapanKobe,