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Archive - Jan 4, 2018


Combination of Oncolytic Virus and Checkpoint Inhibitor Shows Treatment Effectiveness in Mouse Models of Triple-Negative Breast Cancer

The Alliance for Cancer Gene Therapy (ACGT), a non-profit based in Stamford, Connecticut, dedicated to funding breakthrough cancer gene therapy treatments, has had its funding pay off with a promising study on breast cancer coming out of The Ottawa Hospital and the University of Ottawa in Ottawa, Canada. The study suggests that a combination of two immunotherapies -- oncolytic viruses and checkpoint inhibitors -- could be much more successful than traditional treatments in fighting breast cancer and possibly other cancers. The study, which used mouse models, was published in the January 3, 2018 issue of Science Translational Medicine and was conducted by ACGT grantee, Dr. John Bell, and his research lab, in conjunction with Dr. Marie-Claude Bourgeois-Daigneault, lead author of the study and postdoctoral fellow in Dr. Bell's research group. The article is titled “Neoadjuvant Oncolytic Virotherapy Before Surgery Sensitizes Triple-Negative Breast Cancer to Immune Checkpoint Therapy.” Cancer immunotherapy has proven to be a powerful tool in fighting cancer and has revolutionized treatment for cancers such as melanoma and leukemia. Unfortunately though, other forms of cancer, and especially solid tumor cancers, have remained resistant. ACGT has a track record of funding innovative, breakthrough cancer treatments and was one of the initial funders for laboratory research and clinical trials of immunotherapy in support of Dr. Carl June's work at the University of Pennsylvania, where Dr. June’s team has been successfully treating relapsed pediatric leukemia with gene therapy. ACGT started funding cancer cell and gene therapies in the early 2000's when it was still deemed “risky” science.

Adaptive Phage Therapeutics & Progress in Treating Deadly Multidrug-Resistant Bacterial Infections

On April 26, 2017, Adaptive Phage Therapeutics, Inc. (APT), a clinical-stage company founded to provide an effective therapeutic response to the global rise of multi-drug resistant (MDR) pathogenic bacteria, announced that a therapeutic approach leveraging bacteriophage (phage), as outlined in 2003 by NIH Emeritus Scientist, Carl R Merril, MD, (Merril, et al, Nature Reviews; Drug Discovery, 2003) had been used by the University of California-San Diego Medical Center to successfully rescue a terminally ill patient (Tom Patterson) infected with multidrug resistant Acinetobacter baumannii (MDRAB). A detailed story on the use of phage therapy to treat MDR pathogenic bacterial infections was published in the December 25, 2017 issue of Time Magazine ( Titled “Superbugs Are Nearly Impossible to Fight. This Last-Resort Medical Treatment Offers Hope” and authored by Alexandra Sifferlin, the Time story outlines the history of phage-based therapies, which actually dates back almost to the time phage were first discovered (just over 100 years ago). That history is fraught with controversy and mixed results, but great progress in molecular biology and, particularly, the very recent success in the treatment of Tom Patterson, have rekindled interest and hope in this approach to therapy to fight deadly MDR bacterial infections. The Time story also describes the very recent phage-based effort to save the life of 25-year-old Mallory Smith, a cystic fibrosis patient who was in critical condition with a drug-resistant Burkholderia cepacia infection. According to Time, after being notified of Mallory’s plight, APT identified a phage that might be able to kill the bacteria and shipped the virus to the University of Pittsburgh hospital where Mallory was being treated.

Differences in “Silent Code” of Nucleotides (Synonymous Codons), Not Amino Acids, Determine Functions of Actin Isoforms, According to Provocative New Study; Results May Point to Global Form of Functional Regulation

Humans possess six forms of the protein actin that perform essential functions in the body. Two in particular, β-actin and γ-actin, are nearly identical, differing only by four amino acids. Yet these near-twin proteins carry out distinct roles. A long-standing question for biologists has been, how is this possible? "It's a mystery that's been debated in the field for the past 40 years," said Anna Kashina (photo), PhD, a Professor of Biochemistry in the University of Pennsylvania School of Veterinary Medicine (Penn Vet). New findings by Dr. Kashina and colleagues have pointed to a surprising answer. The differing functions of these proteins are determined not by their amino acid sequences but by their genetic code. "We like to call it the 'silent code,'" Dr. Kashina said. "Our findings show that the parts of genes that we think of as being silent actually encode very key functional information." The researchers found that these "silent" differences in the nucleotide sequence seem to influence the density of ribosomes, the molecular machines that translate RNA into proteins. Such differences may enable each individual actin form to take on a different role in the cell. Dr. Kashina coauthored the work, published in the journal eLife, with Penn Vet's Pavan Vedula, Satoshi Kurosaka, Nicolae Adrian Leu, Junling Wang, Stephanie Sterling, and Dawei Dong and the National Institutes of Health's Yuri I. Wolf and Svetlana A. Shabalina. The article is titled “Diverse Functions of Homologous Actin Isoforms Are Defined by Their Nucleotide, Rather Than Their Amino Acid Sequence.” Actin is so ubiquitious and essential that it's known as a "housekeeping protein." It's the most abundant protein in most cells, and its different forms play roles during cell migration, muscle contraction, and development.

ArunA Biomedical Launches New Class of Exosome Biologics to Treat Central Nervous System and Neurodegenerative Disorders; Company Rapidly Moving Toward Clinical Development of Cell-Free Biologic Therapy, Plans to Initiate First-in-Human Studies in 2019

On January 3, 2018, ArunA Biomedical announced the official launch of a new class of cell-free exosome biologics to treat central nervous system and neurodegenerative disorders. With an initial focus on an exosome therapeutic for stroke, the company published, on January 3, 2018, results of a study in Translational Stroke Research that found that extracellular vesicles (EVs) derived from human neural stem cells improved tissue and functional recovery in murine thromboembolic stroke models. The open-access article is titled “Human Neural Stem Cell Extracellular Vesicles Improve Tissue and Functional Recovery in the Murine Thromboembolic Stroke Model.” The study was led by Dr. Steven Stice, a Georgia Research Alliance Eminent Scholar endowed chair, Professor and Director of the Regenerative Bioscience Center at The University of Georgia, and who serves as Co-Founder, Chief Executive, and Chief Scientific Officer for ArunA Biomedical. The study was conducted in collaboration with Dr. Nasrul Hoda at Augusta University in Augusta, Georgia. Neural stem cells (NSCs) and mesenchymal stem cells (MSCs) were evaluated for changes in infarct volume as well as sensorimotor function. Results showed that the NSC EVs improved cellular, tissue, and functional outcomes in middle-aged rodents, whereas MSC EVs were less effective. Acute differences in lesion volume following NSC EV treatment were corroborated by MRI in aged rodents. NSC EVs mechanistically increased circulating regulatory T cell numbers, which are known to enhance remyelination in the injured brain. Specifically, neural stem cell EV treatment has a positive effect on motor function as indicated by beam walk, instances of foot faults, and strength evaluated by a hanging wire test.