Volume 16.35 | Sep 21

Issue 16.35 September 21, 2015
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TOP STORY
Delivering Missing Protein Heals Damaged Hearts in Animals
Scientists have enabled damaged heart tissue in animals to regenerate by delivering a protein to it via a bioengineered collagen patch. They set out to reintroduce Fstl1 back into the damaged epicardial tissue of mice and pigs that had suffered a heart attack. Within two to four weeks of receiving the patch, heart muscle cells began to proliferate and the animals progressively recovered heart function. [Press release from Stanford Medicine discussing online prepublication in Nature] Press Release | Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
Combined Inhibition of BET Family Proteins and Histone Deacetylases as a Potential Epigenetics-Based Therapy for Pancreatic Ductal Adenocarcinoma
Scientists showed that JQ1, an inhibitor of the bromodomain and extraterminal (BET) family of proteins, suppresses pancreatic ductal adenocarcinoma (PDAC) development in mice by inhibiting both MYC activity and inflammatory signals. Using a CRISPR-Cas9–based method for gene editing directly in the mouse adult pancreas, they showed that de-repression of p57 upon combined BET and histone deacetylase inhibition is required for the induction of combination therapy–induced cell death in PDAC. [Nat Med] Abstract | Press Release

3D Printed Anatomical Nerve Regeneration Pathways
In vivo studies examining the regeneration of bifurcated injuries across a 10 mm complex nerve gap in rats showed that the 3D printed scaffolds achieved successful regeneration of complex nerve injuries, resulting in enhanced functional return of the regenerated nerve. [Adv Funct Mater] Abstract | Press Release | Video

GITR Subverts Foxp3+ Tregs to Boost Th9 Immunity through Regulation of Histone Acetylation
Researchers demonstrated that glucocorticoid-induced TNFR-related protein (GITR) ligation subverts the induction of Foxp3+ regulatory T cells (Tregs) and directs the activated CD4+ T cells to Th9 cells. Such GITR-mediated iTreg to Th9 induction enhances anti-tumor immunity in vivo. [Nat Commun] Full Article | Press Release

Copy Number Variations of HLA-I and Activation of NKp30 Pathway Determine the Sensitivity of Gastric Cancer Cells to the Cytotoxicity of Natural Killer Cells
Researchers found that the tumorigenic capacity of human gastric cancer cell lines was dependent on the recruitment and activation of natural killer (NK) cells in xenograft tumors. Treatment of tumor bearing mice with systemic administration of interleukin-12 in combination with intratumor injection of anti-HLA-I antibody significantly increased NK cell recruitment into xenograft tumors, which became sensitive to NK killing, resulting in reduced tumor progression. [Oncogene] Abstract

The Nuclear Orphan Receptor NR2F6 Is a Central Checkpoint for Cancer Immune Surveillance
Scientists showed that genetic ablation of nuclear receptor subfamily 2, group F, member 6 (Nr2f6) significantly improves survival in the murine transgenic TRAMP prostate cancer model. Furthermore, Nr2f6−/− mice spontaneously reject implanted tumors and develop host-protective immunological memory against tumor rechallenge. [Cell Rep] Full Article | Graphical Abstract

Altered Immunogenicity of Donor Lungs via Removal of Passenger Leukocytes Using Ex Vivo Lung Perfusion
Investigators utilized ex vivo lung perfusion (EVLP) to study passenger leukocyte migration from donor lungs into the recipient and to evaluate the effects of donor leukocyte depletion prior to transplantation. Female pigs received male left lungs either following three hours of EVLP or retrieved using standard protocols. EVLP-reduced donor leukocyte transfer into the recipient and migration to recipient lymph nodes was markedly reduced. [Am J Transplant] Abstract | Press Release

Patient-Individualized CD8+ Cytolytic T-Cell Therapy Effectively Combats Minimal Residual Leukemia in Immunodeficient Mice
Scientists analyzed graft-versus-leukemia responses of acute myeloid leukemia-reactive CD8+ cytolytic T-lymphocytes with central and effector memory phenotype in a new allogeneic donor-patient specific humanized mouse model. [Int J Cancer] Abstract

Human Fused NKG2D–IL-15 Protein Controls Xenografted Human Gastric Cancer through the Recruitment and Activation of NK Cells
Researchers transplanted human gastric cancer cells into nude mice and mouse melanoma cells with ectopic expression of major histocompatibility complex class I chain-related protein A into C57BL/6 mice. Then, they studied the anti-tumor effects mediated by dsNKG2D–IL-15 in the two xenografted tumor models. [Cell Mol Immunol] Abstract

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REVIEWS
siRNA versus miRNA as Therapeutics for Gene Silencing
The authors provide a comparison between therapeutic small interfering RNAs (siRNAs) and microRNAs (miRNAs) in terms of their mechanisms of action, physicochemical properties, delivery, and clinical applications. Moreover, the challenges in developing both classes of RNA as therapeutics are also discussed. [Mol Ther Nucleic Acids] Full Article

Cellular Engineering and Therapy in Combination with Cord Blood Allografting in Pediatric Recipients
Early and preliminary results suggest some experimental cellular strategies may in part ameliorate the incidence of primary graft failure, delays in hematopoietic reconstitution and/or slowness in cellular immune reconstitution following unrelated cord blood transplantation. [Bone Marrow Transplant] Abstract

Visit our reviews page to see a complete list of reviews in the cell, gene and immunotherapy research fields.

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SCIENCE NEWS
TxCell to Present Its Cellular Immunotherapy Developments at Leading Cell and Ophthalmology Conferences
TxCell SA announced that Dr. Miguel Forte, chief operating officer, and Dr. Arnaud Foussat, chief scientific officer of TxCell, will present at three forthcoming leading cell and gene therapy and ophthalmology conferences. [Press release from TxCell SA discussing research to be presented at the International Society of Cellular Therapy (ISCT) Europe 2015 Regional Meeting, Seville; Phacilitate Cell & Gene Therapy Europe, Barcelona; and the European Association for Vision and Eye Research (EVER) 2015 Congress, Nice] Press Release

Cellular Biomedicine Group to Present CAR-T Phase I Clinical Trial Data for Non Small Cell Lung Cancer and Other Solid Tumors
Cellular Biomedicine Group Inc. announced that it would give an oral presentation to discuss Phase I clinical trial data for EGFR (HER-1)-targeted chimeric antigen receptor-modified T-cells (CAR-T) immunotherapy for patients with non-small cell lung cancer and other solid tumors. [Press release from Cellular Biomedicine Group Inc. discussing research to be presented at the 5th World Congress on Cancer Therapy, Atlanta] Press Release

PharmaMar Showcases New Data for YONDELIS® and PM1183 in Soft Tissue Sarcoma and Solid Tumors
PharmaMar announced that it will show new data from clinical pivotal studies as well as real-life data from prospective non-interventional studies to highlight the role of YONDELIS® (trabectedin) in soft tissue sarcoma. [Press release from PharmaMar discussing research to be presented at the European Cancer Congress (ECC) 2015, Vienna] Press Release

Penn Team Pinpoints Immune Changes in Blood of Melanoma Patients on PD-1 Drugs that Put Potential Biomarker within Reach
A simple blood test can detect early markers of “reinvigorated” T cells and track immune responses in metastatic melanoma patients after initial treatment with the anti-PD-1 drug pembrolizumab. [Press release from Penn Medicine discussing research presented at CRI-CIMT-EATI-AACR – The Inaugural International Cancer Immunotherapy Conference, New York] Press Release

Identifying Protein that May Predict Response to PD-1 Immunotherapy for Melanoma
Mayo Clinic researchers have identified a protein marker whose frequency may predict patient response to PD-1 blockade immunotherapy for melanoma. [Press release from Mayo Clinic discussing research presented at CRI-CIMT-EATI-AACR – The Inaugural International Cancer Immunotherapy Conference, New York] Press Release | Video

Five Prime Therapeutics’ Phase Ia/Ib Trial of FPA008 and OPDIVO (Nivolumab) Featured as a Trial-in-Progress
Five Prime Therapeutics, Inc. announced that the Phase Ia/Ib clinical trial combining FPA008 with OPDIVO® in multiple tumor types was featured in a trial-in-progress poster. [Press release from Five Prime Therapeutics, Inc. discussing research presented at CRI-CIMT-EATI-AACR – The Inaugural International Cancer Immunotherapy Conference, New York] Press Release

BGB324 Enhances Immune Checkpoint Inhibitor Efficacy in Preclinical Cancer Models
BerGenBio AS has announced new preclinical data on lead compound, BGB324, in combination with immune checkpoint inhibitors, has been presented as a poster. [Press release from BerGenBio AS discussing research presented at CRI-CIMT-EATI-AACR – The Inaugural International Cancer Immunotherapy Conference, New York] Press Release

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POLICY
UK Scientists Apply for License to Edit Genes in Human Embryos
Scientists in London have asked for permission to edit the genomes of human embryos — a request that could lead to the world’s first approval of such research by a national regulatory body. Kathy Niakan, a researcher affiliated with the Francis Crick Institute, said that she is proposing to use gene editing to provide “fundamental insights into early human development.” [Nature News] Editorial

Canadian Election Spotlights Scientists’ Frustrations
Canadians will head to the polls on October 19th, in a federal election that many scientists hope will mark a turning point after years of declining research budgets and allegations of government censorship. Although science has not emerged as a top issue during the campaign, researchers are fighting to make their concerns heard. [Nature News] Editorial

Australia Gets a New Science Minister
Australia has a new science minister. Christopher Pyne, a lawyer and veteran politician who has been serving as the conservative government’s education minister, was sworn in to his new post as part of a reshuffle by new Prime Minister Malcolm Turnbull. Many Australian researchers say they hope Pyne’s appointment will mark a turn in policy under Turnbull. [ScienceInsider] Editorial

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BUSINESS
Seattle Children’s Research Institute Teams Up with bluebird bio to Pioneer Genome Editing and Gene Therapy Research in Pediatric Diseases
A new collaboration between Seattle Children’s Research Institute and bluebird bio, Inc. will allow researchers to develop potentially transformative gene therapies for severe genetic and rare diseases. bluebird bio will provide a total of up to $3 million over three years to sponsor research performed at the Seattle Children’s Research Institute Center for Immunity and Immunotherapies. [Seattle Children’s Research Institute] Press Release

Amgen and Xencor Announce Strategic Collaboration in Cancer Immunotherapy and Inflammation
Amgen and Xencor, Inc. announced that the two companies have entered into a research and license agreement to develop and commercialize novel therapeutics in the areas of cancer immunotherapy and inflammation. [Amgen Inc.] Press Release

Antibody Network Partners with Celgene for Cancer Therapies
A new collaboration between Celgene Corp. and the Recombinant Antibody Network, a consortium comprising research groups from UC San Francisco, the University of Chicago and the University of Toronto, will support the development of next-generation, antibody-based cancer therapies. [UC San Francisco] Press Release

Van Andel Research Institute, Los Alamos National Laboratory to Develop Detailed Computational Model to Study Lung Cancer
A multidisciplinary team, led by Jeffrey MacKeigan, Ph.D., associate professor at Van Andel Research Institute in collaboration with William Hlavacek, Ph.D., of Los Alamos National Laboratory, is designing a mathematical model for autophagy in lung cancer that will be used to develop novel cancer treatment strategies. [Los Alamos National Laboratory] Press Release

UI Cystic Fibrosis Researchers Receive $11 Million Grant Renewal for Gene Therapy Work
Researchers in the University of Iowa Pappajohn Biomedical Institute have received a five-year, $11 million grant from the National Heart, Lung, and Blood Institute, part of the National Institutes of Health, to continue advancing gene therapy to treat and prevent cystic fibrosis, a life-shortening, lethal lung disease. [University of Iowa] Press Release

UI Researchers Receive First-in-the-Nation Grant to Study Neuroendocrine Tumors
Researchers at the University of Iowa Holden Comprehensive Cancer Center have received the first-ever Specialized Programs of Research Excellence (SPORE) grant to study neuroendocrine tumors. The five-year, $10.67 million grant is the only SPORE grant funding research on neuroendocrine tumors. [University of Iowa] Press Release

Extreme Makeover of the Heart: Matrix Therapy Is First FDA-Approved Procedure of Its Kind
A cardiovascular team has successfully performed a first-in-the-world heart procedure on a 72-year-old attorney after suffering a large heart attack. Amit N. Patel, M.D. M.S. was the first physician to perform an emerging heart procedure where cardiac matrix is directly injected into a damaged heart. This is the first clinical trial to be approved by the U.S. Food and Drug Administration (FDA) for matrix therapy of the heart. [University of Utah Hospital] Press Release

Cancer Treatment Centers of America at Western Regional Medical Center Launches Next Phase of Immunotherapy Clinical Trial Aimed at Soft-Tissue Cancers
Cancer Treatment Centers of America® at Western Regional Medical Center has begun the Phase II of another arm of its multi-arm clinical trial that combines immunotherapy with chemotherapy. This arm was specifically designed to target soft-tissue cancers. [Cancer Treatment Centers of America Inc.] Press Release
 
NIH
National Heart, Lung, and Blood Institute; Notice of Closed Meeting (FR Doc. No: 2015-23505)
 
CBER
Formal Dispute Resolution: Appeals above the Division Level; Revised Draft Guidance for Industry and Review Staff; Availability
 
REGULATORY
Food and Drug Administration (United States)

Product-Specific Bioequivalence Recommendations; Draft and Revised Draft Guidances for Industry; Availability (FR Doc. No: 2015-23571)

Vaccines and Related Biological Products Advisory Committee; Notice of Meeting (FR Doc. No: 2015-23550)
 
EVENTS
NEW AABB Annual Meeting 2015
October 24-27, 2015
Anaheim, United States

NEW 2nd Annual Matrix Biology Ireland (MBI) Meeting 2015
December 2-4, 2015
Dublin, Ireland

NEW Clinical Applications of Stem Cells
February 24-25, 2016
Singapore, Singapore

Visit our events page to see a complete list of events in the cell, gene and immunotherapy community.
 
JOB OPPORTUNITIES
NEW Assistant Professor – Stem Cell Biology (University of South Carolina)

NEW Senior Stem Cell Scientist (Medicines and Healthcare products Regulatory Agency)

Postdoctoral Researcher – Epigenetic Modifiers (Van Andel Research Institute)

Senior Cell Biologist (Adaptimmune Inc.)

Postdoctoral Fellow – Immunotherapy/T Cell Biology (California Institute for Biomedical Research)

Postdoctoral Position – Spinal Cord Injury Research (Indiana University-Purdue University)

Postdoctoral Fellow – HMGA Chromatin Remodeling Proteins in Cancer and Stem Cell Biology (Johns Hopkins University School of Medicine)

Postdoctoral Fellow Position – Genome Editing, Synthetic Biology, and Cell Evolution and Engineering (University of California – Irvine)

Research Associate – Cell Biology (Editas Medicine)

Senior Research Associate (Editas Medicine)

Cell Biology Lab Manager (Harvard Apparatus Regenerative Technology)

Science Writer – Cardiovascular Regeneration (Houston Methodist Research Institute)

Aseptic Manufacturing Associate (Lonza Biologics, Inc.)


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