Cell Therapy News Volume 18.06 | Feb 27 2017

TOP STORY

Targeting a CAR to the TRAC Locus with CRISPR/Cas9 Enhances Tumor Rejection

Investigators showed that directing a CD19-specific chimeric antigen receptor (CAR) to the T-cell receptor α constant (TRAC) locus not only results in uniform CAR expression in human peripheral blood T cells, but also enhances T-cell potency, with edited cells vastly outperforming conventionally generated CAR T cells in a mouse model of acute lymphoblastic leukemia. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Clonal Hematopoiesis Associated with TET2 Deficiency Accelerates Atherosclerosis Development in Mice

The authors studied the effects of the expansion of Tet2-mutant cells in atherosclerosis-prone, low-density lipoprotein receptor–deficient mice. They found that partial bone marrow reconstitution with TET2-deficient cells was sufficient for their clonal expansion and led to a marked increase in atherosclerotic plaque size. TET2-deficient macrophages exhibited an increase in NLRP3 inflammasome–mediated interleukin-1β secretion. [Science] Abstract

Ionic Colloidal Molding as a Biomimetic Scaffolding Strategy for Uniform Bone Tissue Regeneration

Scientists demonstrated that carboxyl functionalization of poly(lactic-co-glycolic acid) can achieve great material homogeneity in nanocomposites. This ionic colloidal molding method stabilizes hydroxyapatite precursors to confer even nanodopant packing, improving therapeutic outcomes in bone repair by remarkably improving mechanical properties of nanocomposites and optimizing controlled drug release, resulting in better cell in-growth and osteogenic differentiation. [Adv Mater] Abstract

Systemic Delivery of Factor IX Messenger RNA for Protein Replacement Therapy

Safe and efficient delivery of messenger RNAs for protein replacement therapies offers great promise but remains challenging. Investigators demonstrated systemic, in vivo, nonviral mRNA delivery through lipid nanoparticles to treat a Factor IX-deficient mouse model of hemophilia B. [Proc Natl Acad Sci USA] Full Article

Armed Oncolytic Adenovirus Expressing PD-L1 Mini-Body Enhances Anti-Tumor Effects of Chimeric Antigen Receptor T-Cells in Solid Tumors

Researchers evaluated, in human tumor xenograft models, the pro-inflammatory properties of an oncolytic adenovirus with a helper-dependent Ad that expresses a PD-L1 blocking mini-antibody, as a strategy to enhance CAR T-cell killing. Co-administration of these agents exhibited oncolytic effects with production of PD-L1 mini-body locally at the tumor site. [Cancer Res] Abstract

The Balance between CD8⁺ T Cell-Mediated Clearance of AAV Encoded Antigen in the Liver and Tolerance Is Dependent on the Vector Dose

Researchers found that hepatic transfer of limited doses of an adeno-associated virus (AAV)-ovalbumin vector rapidly induced antigen-specific CD8⁺ T cells that only became functionally competent after greater than two months. At this time, CD8⁺ T cells had down-regulated negative checkpoint markers, e.g. the Programmed Death 1 receptor, and up-regulated expression of relevant cytokines. [Mol Ther] Abstract

Follistatin Gene Therapy for Sporadic Inclusion Body Myositis Improves Functional Outcomes

For this clinical trial rAAV1.CMV.huFS344, 6 X1011 vg/kg was delivered to the quadriceps muscle of both legs of six sporadic inclusion body myositis subjects. The primary outcome for this trial was distance traveled for the 6 Minute Walk Test. [Mol Ther] Abstract

Suppressor of Cytokine Signaling-1 Gene Therapy Induces Potent Antitumor Effect in Patient-Derived Esophageal Squamous Cell Carcinoma Xenograft Mice

Chronic inflammation is involved in cancer growth in esophageal squamous cell carcinoma (ESCC), which is a highly refractory cancer with poor prognosis. Researchers investigated the antitumor effect and mechanisms of SOCS1 gene therapy for ESCC. Patients with ESCC showed epigenetics silencing of SOCS1 gene by methylation in the CpG islands. [Int J Cancer] Abstract

Modulation of Digital Flexor Tendon Healing by Vascular Endothelial Growth Factor Gene Transfection in a Chicken Model

The authors investigated the effects of vascular endothelial growth factor (VEGF) genes delivered by adeno-associated virus (AAV) vectors on tendon healing and molecular events involved in a chicken model. One hundred and twenty eight deep flexor tendons in the long toes of chickens were completely transected and injected with 2 × 109 particles of AAV2-VEGF or saline before surgically repaired. [Gene Ther] Abstract

Tracking the Fate and Origin of Clinically Relevant Adoptively Transferred CD8⁺ T Cells In Vivo

Scientists applied high-throughput T cell receptor Vβ sequencing to identify individual clonotypes within cytotoxic T cells products, track them in vivo after infusion, and then deduce the preadoptive transfer frequencies of cells ultimately responsible for tumor regression. [Sci Immunol] Abstract

Cellular Uptake and Trafficking of Antisense Oligonucleotides

Antisense oligonucleotides (ASOs) modified with phosphorothioate (PS) linkages and different 2′ modifications can be used either as drugs or as research tools to alter gene expression. PS-ASOs can enter cells without additional modification or formulation and can be designed to mediate sequence-specific cleavage of different types of RNA targeted by endogenous RNase H1. [Nat Biotechnol] Abstract

Hematopoietic Stem Cell Transplantation for Autoimmune Diseases

The authors discuss the immunological mechanisms of hematopoietic stem cell transplantation (HSCT) in various autoimmune diseases and current HSCT regimens. After carefully taking into consideration the risks and benefits of HSCT and alternative therapies, they also discuss the efficacy, complications and proposed indications of this procedure. [Nat Rev Rheumatol] Abstract

Allogeneic Hematopoietic Cell Transplantation in Patients with AML Not Achieving Remission: Potentially Curative Therapy

The authors summarize existing data on allogeneic hematopoietic cell transplantation in patients with refractory or relapsed acute myeloid leukemia and explore novel approaches with the potential to improve outcomes in this patient population. [Bone Marrow Transplant] Abstract

Visit our reviews page to see a complete list of reviews in the cell therapy research field.

Takeda and TiGenix Report New Data Highlighting Maintenance of Long-Term Remission of Complex Perianal Fistulas in Crohn’s Disease Patients with Cx601

Takeda Pharmaceutical Company Limited and TiGenix NV announced new data from the Phase III ADMIRE-CD clinical trial, which indicated that investigational compound Cx601, a suspension of allogeneic adipose-derived stem cells, maintained long-term remission of treatment refractory complex perianal fistulas in patients with Crohn’s disease over 52 weeks. [Press release from TiGenix NV discussing research presented at the 12^th Congress of the European Crohn’s and Colitis Organization, Barcelona] Press Release (Download)

Fate Therapeutics and Regents of the University of Minnesota Expand Research Collaboration for Clinical Translation of Engineered iPSC-Derived Natural Killer Cell Cancer Immunotherapy

Fate Therapeutics, Inc. announced an expansion of its research collaboration with the Regents of the University of Minnesota to initiate the clinical translation of a first-of-kind product candidate, an off-the-shelf targeted natural killer cell cancer immunotherapy derived from an engineered induced pluripotent stem cell (iPSC) line. [Fate Therapeutics, Inc.] Press Release

CBMG Awarded $2.29 Million Grant from the California Institute for Regenerative Medicine

Cellular Biomedicine Group Inc. (CBMG) announced that the governing Board of the California Institute for Regenerative Medicine, California’s stem cell agency, has awarded the company $2.29 million to support pre-clinical studies of AlloJoin^TM, CBMG’s “Off-the-Shelf” Allogeneic Human Adipose-derived Mesenchymal Stem Cells for the treatment of Knee Osteoarthritis in the United States. [Cellular Biomedicine Group Inc.] Press Release

Beyond Type 1 Provides Grant to ViaCyte to Support Research and Development of Cell Replacement Therapies for Type 1 Diabetes

ViaCyte, Inc. and Beyond Type 1 announced a grant from Beyond Type 1 to support ViaCyte’s efforts to develop a functional cure for type 1 and other insulin-requiring diabetes. The company’s pluripotent stem cell-derived islet cell replacement therapy, the PEC-Direct^™ product candidate, has the potential to be a breakthrough treatment for high-risk type 1 diabetes. [ViaCyte, Inc.] Press Release

Merck’s Letermovir, an Investigational Antiviral Medicine for Prevention of Cytomegalovirus (CMV) Infection in Bone Marrow Transplant Recipients, Highly Effective through Week 24 Post-Transplant in Pivotal Phase III Study

Merck & Co., Inc. announced results of the pivotal Phase III clinical study of letermovir, an investigational antiviral medicine for the prevention of clinically-significant CMV infection in adult CMV-seropositive recipients of an allogeneic hematopoietic stem cell transplant (HSCT), also known as bone marrow transplant. The study met its primary efficacy endpoint, showing that significantly fewer patients with undetectable CMV DNA at the start of study treatment developed clinically significant CMV infection through Week 24 post-HSCT. [Merck & Co., Inc.] Press Release

OncoSec Granted FDA Fast Track Designation for ImmunoPulse^® IL-12 for the Treatment of Metastatic Melanoma following Progression on Pembrolizumab or Nivolumab

OncoSec Medical Incorporated received Fast Track designation from the U.S. Food and Drug Administration (FDA) for its ImmunoPulse^® IL-12, a potentially first-in-class, Intratumoral anti-cancer gene therapy that expresses interleukin-12 (IL-12) for the treatment of metastatic melanoma, following progression on pembrolizumab or nivolumab. [OncoSec Medical Incorporated] Press Release

Sangamo Therapeutics Receives Rare Pediatric Disease Designation from FDA For SB-318 In Vivo Genome Editing Therapeutic for MPS I

Sangamo Therapeutics, Inc. announced that the U.S. Food and Drug Administration (FDA) has granted rare pediatric disease designation for SB-318, the company’s in vivo genome editing product candidate for the treatment of Mucopolysaccharidosis Type I (MPS I), a lysosomal storage disorder. [Sangamo Therapeutics, Inc.] Press Release

U.S. Patent for Urocortin 2 Gene Constructs Issued

Renova^™ Therapeutics announced that a patent for constructs and compositions containing the urocortin 2 gene, its analogs and uses thereof has issued in the United States. Renova Therapeutics holds an exclusive worldwide license to this patent from the nonprofit Research Development Foundation. [Renova^™ Therapeutics] Press Release

BrainStorm Seeking Approval to Distribute NurOwn^® in Canada

BrainStorm Cell Therapeutics Inc. has signed an agreement with CCRM to support the market authorization request for NurOwn^®. At this time, CCRM is helping Brainstorm explore the opportunity to access Health Canada’s early access pathway for treatment of patients with Amyotrophic Lateral Sclerosis. [BrainStorm Cell Therapeutics Inc.] Press Release

Imanis Life Sciences Launches Line of Oncolytic Vaccinia Viruses from Genelux Corporation

Imanis Life Sciences announced the launch of a new product line of oncolytic vaccinia viruses for virotherapy research. These viruses are licensed from Genelux Corporation as part of Genelux’s proprietary, vaccinia virus-based technology platform for research use. [Imanis Life Sciences] Press Release

REVLIMID^® (Lenalidomide) Approved by the European Commission as Monotherapy for the Maintenance Treatment of Patients with Newly Diagnosed Multiple Myeloma after Autologous Stem Cell Transplantation

Celgene International Sàrl announced that the European Commission has approved REVLIMID^® as monotherapy for the maintenance treatment of adult patients with newly diagnosed multiple myeloma who have undergone autologous stem cell transplantation. REVLIMID^® is the first and only licensed maintenance treatment available to these patients. [Celgene International Sàrl] Press Release

Aptinyx Chief Scientific Officer Joseph Moskal, Ph.D. Named Fellow by National Academy of Inventors and the American Institute for Medical and Biological Engineering

Aptinyx Inc. announced that Joseph Moskal, Ph.D., chief scientific officer, has been elected to the 2016 class of Fellows of the National Academy of Inventors, and also has been elected to the College of Fellows for the American Institute for Medical and Biological Engineering. [Aptinyx Inc.] Press Release

Two Top Chinese-American Scientists Have Dropped Their U.S. Citizenship

Two top Chinese scientists, one a Nobel laureate and the other a winner of a top computer science prize, have renounced their U.S. citizenship to become citizens of China. [ScienceInsider] Editorial

U.S. Researchers Guilty of Misconduct Later Won More than $100 Million in NIH Grants, Study Finds

Many believe that once a scientist is found guilty of research misconduct, his or her scientific career is over. But a new study suggests that, for many U.S. researchers judged to have misbehaved, there is such a thing as a second chance. [ScienceInsider] Editorial

Biologists Propose to Sequence the DNA of All Life on Earth

At a meeting organized by the Smithsonian Initiative on Biodiversity Genomics and the Shenzhen, China–based sequencing powerhouse BGI, a small group of researchers upped the ante even more, announcing their intent to, eventually, sequence “all life on Earth.” [ScienceInsider] Editorial

FDA

Current State and Further Development of Animal Models of Serious Infections Caused by Acinetobacter baumannii and Pseudomonas aeruginosa; Public Workshop (FR Doc. No:2017-03751) Notice

Pediatric Postmarketing Pharmacovigilance and Drug Utilization Reviews; Establishment of a Public Docket; Request for Comments (FR Doc. No:2017-03365) Notice

NEW 2^nd International Conference on Stem Cells
September 27-October 2, 2017
Rhodes, Greece

Visit our events page to see a complete list of events in the community.

NEW Principle Investigator and Postdoctoral Positions – Various Projects (Guangzhou Women and Children’s Medical Center (GWCMC) – Sun Yat-Sen University)

NEW BIH Chair for Cell and Gene Therapy and Coordinator of the Advanced Therapies Program (Berlin Institute of Health (BIH))

Postdoctoral Positions – Stem Cell Research (Indian Institute of Science Education and Research Thiruvananthapuram)

Assistant Professor – Medicine by Design Junior Chair in Immunobioengineering (University of Toronto)

Associate/Full Professor – Loretta Rogers Chair in Immunobioengineering (University of Toronto)

Medical Director – Clinical Research Physician (Celgene Corporation)

Postdoctoral Fellow – Various Projects (University of Oklahoma)

Scientist – Regulatory Support (Cook MyoSite, Inc.)

Tenure Track Faculty – Stem Cells and Regenerative Medicine (University of Notre Dame)

Staff Research Associate III – Translational Research to Clinical Cell Therapies (University of California Davis Health System)

Laboratory Technician – Cellular Production Associate II-III (Fred Hutchinson Cancer Research Center)

GMP Manufacturing Director – Cell and Gene Therapy (Fred Hutchinson Cancer Research Center)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

Assistant or Associate Member – Stem CellGene Therapy (Fred Hutchinson Cancer Research Center)

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