Human Immunology News Volume 8.01 | Jan 14 2020

TOP STORY

Clonally Expanded CD8 T Cells Patrol the Cerebrospinal Fluid in Alzheimer’s Disease

Researchers performed mass cytometry of peripheral blood mononuclear cells and discovered an immune signature of Alzheimer’s disease that consists of increased numbers of CD8⁺ T effector memory CD45RA⁺ cells. In a second cohort, they found that CD8⁺ TEMRA cells were negatively associated with cognition. [Nature] Abstract

(Ranked by impact factor of the journal)

Clonal Kinetics and Single-Cell Transcriptional Profiling of CAR-T Cells in Patients Undergoing CD19 CAR-T Immunotherapy

Investigators performed TCRB sequencing, integration site analysis, and single-cell RNA sequencing to profile CD8⁺ CAR-T cells from infusion products and blood of patients undergoing CD19 CAR-T immunotherapy. TCRB sequencing showed that clonal diversity of CAR-T cells is highest in the infusion products and declines following infusion. [Nat Commun] Full Article

Neutrophil Extracellular Trap-Associated RNA and LL37 Enable Self-Amplifying Inflammation in Psoriasis

The authors showed here that primary murine and human neutrophils (PMNs) mount a fulminant and self-propagating neutrophil extracellular trap (NET) and cytokine response, but independently of the canonical NET component, DNA. Unexpectedly, RNA, which was abundant in NETs and psoriatic but not healthy skin, in complex with LL37 triggered TLR8/TLR13-mediated cytokine and NET release by PMNs in vitro and in vivo. [Nat Commun] Full Article

Hepatitis B Virus Particles Activate Toll-Like Receptor 2 Signaling Initial Upon Infection of Primary Human Hepatocytes

The authors investigated cellular changes after the first-contact between hepatitis B virus (HBV) and primary human hepatocytes (PHH) in vitro and in vivo. The exposure of PHH to HBV particles resulted in nuclear translocation of NFκB, followed by the expression and secretion of inflammatory cytokines. [Hepatology] Abstract

CD4⁺ T Follicular Helper Cells in Human Tonsils and Blood Are Clonally Convergent but Divergent From Non-Tfh CD4⁺ Cells

Using donor-matched blood and tonsil samples, scientists investigated T cell receptor sharing between tonsillar T follicular helper (Tfh) cells and peripheral Tfh and non-Tfh cell populations. TCR transcript sequencing revealed considerable clonal overlap between peripheral and tonsillar Tfh cell subsets as well as a clear distinction between Tfh and non-Tfh cells. [Cell Rep] Full Article | Graphical Abstract

Human iPSC-Derived Neural Crest Stem Cells Exhibit Low Immunogenicity

Scientists assessed the expression of immune-related antigens in iPSC-neural crest stem cells (NSCs), including HLA class I and II and co-stimulatory molecules. To investigate functional immunogenicity, iPSC-NCSCs were used as stimulator cells in a one-way mixed lymphocyte reaction. [Mol Ther Methods Clin Dev] Abstract

Staphylococcus aureus PSMα3 Cross-α Fibril Polymorphism and Determinants of Cytotoxicity

The authors demonstrated that massive T cell deformation and death are linked with PSMα3 aggregation and co-localization with cell membranes. The extensive mutagenesis analyses support the role of positive charges, and especially Lys17, in interactions with the membrane and suggest their regulation by inter- and intra-helical electrostatic interactions within the cross-α fibril. [Structure] Full Article | Download Graphical Abstract

Melanoma Cell-Derived Exosomes in Plasma of Melanoma Patients Suppress Functions of Immune Effector Cells

Plasma exosomes were isolated and separated by immunocapture into two fractions: melanoma cell-derived exosomes (MTEX) and normal cell-derived exosomes (non-MTEX). Immunosuppressive effects of MTEX on primary human immune cells were evaluated. Exosomes were isolated from plasma of 12 melanoma patients and six healthy donors. [Sci Rep] Full Article

Enhanced Formation of Neutrophil Extracellular Traps in Kawasaki Disease

After neutrophils isolated from the peripheral blood of patients with KD and healthy children were cultured in vitro, the degree of spontaneous NETosis was evaluated by measuring the number of NETs formed and the titers of cell-free DNA and neutrophil elastase-DNA complex. [Pediatr Res] Abstract

Subscribe to our sister publications: Immunology of Infectious Disease News & Immune Regulation News.

Immune Checkpoint Imaging in Oncology – a Game Changer Towards Personalized Immunotherapy?

At present, checkpoint-specific molecular imaging is increasingly investigated as a tool for patient selection and response evaluation. Here, an overview of the current developments in immune checkpoint imaging is provided. [J Nucl Med] Abstract

Human iPSC-Derived Microglia: A Growing Toolset to Study the Brain’s Innate Immune Cells

The authors discuss the variety of research applications that different techniques enables and to highlight recent discoveries that these methods have begun to uncover. By presenting the research paradigms in which each model has been successful, as well as the key benefits and limitations of each approach, they hope that this review will help interested researchers to incorporate these techniques into their studies, collectively advancing our understanding of human microglia biology. [Glia] Abstract

Visit our reviews page to see a complete list of reviews in the human immunology research field.

Astellas and Adaptimmune Enter into Agreement to Co-Develop and Co-Commercialize Stem-Cell Derived Allogeneic CAR-T and TCR T-Cell Therapies

Astellas Pharma Inc. through its wholly-owned subsidiary Universal Cells, Inc. and Adaptimmune Therapeutics plc announced that they have entered into a co-development and co-commercialization agreement to bring new stem-cell derived allogeneic T-cell therapies to people with cancer. [Astellas Pharma Inc.] Press Release

BridgeBio Pharma’s Gene Therapy Subsidiaries Enter Strategic Partnership with Catalent for Dedicated Gene Therapy Development and Manufacturing Capacity

BridgeBio Pharma, Inc. announced a collaboration agreement with Catalent to establish dedicated gene therapy development and manufacturing capacity at Catalent’s Paragon Gene Therapy clinical and commercial manufacturing center in Harmans, Maryland. The agreement is intended to support the clinical and commercial manufacturing needs for BridgeBio’s gene therapy product candidates for congenital adrenal hyperplasia, BBP-631, and Canavan disease, BBP-812. [BridgeBio Pharma, Inc.] Press Release

Indapta Therapeutics and Lonza Announce Strategic Partnership to Advance a Next-Generation, Off-the-Shelf, Allogeneic Immuno-Oncology Therapy

Indapta Therapeutics, Inc. Lonza announced a strategic partnership. Indapta also announced its founding leadership team and scientific advisors. Under the terms of the agreement, Lonza will manufacture Indapta’s off-the-shelf, allogeneic G-NK cell therapy under current good manufacturing practices for use in clinical studies. [Lonza] Press Release

CYTOVIA Therapeutics and the New York Stem Cell Foundation Research Institute Enter into a Partnership to Develop iPSC Derived CAR NK Therapeutics

The New York Stem Cell (NYSCF) Foundation Research Institute announced a partnership with Cytovia Therapeutics Inc. to develop new disease treatments that leverage human stem cell research and novel gene editing techniques. NYSCF will be a key partner to Cytovia in using stem cells to advance novel therapeutic targets for cancer. [The New York Stem Cell] Press Release

Tacitus Therapeutics Launches in Collaboration with Mount Sinai to Develop Stem Cell Therapies for Life-Threatening Diseases

Tacitus Therapeutics has launched in collaboration with the Mount Sinai Health System to develop stem cell therapies initially targeting blood cancers and related clotting disorders. Their first therapy, HSC100, currently is being investigated in a Phase I clinical trial. [Tacitus Therapeutics] Press Release

Indapta Therapeutics and Lonza Announce Strategic Partnership to Advance a Next-Generation, Off-the-Shelf, Allogeneic Immuno-Oncology Therapy

Indapta Therapeutics, Inc and Lonza announced a strategic partnership. Indapta also announced its founding leadership team and scientific advisors. Under the terms of the agreement, Lonza will manufacture Indapta’s off-the-shelf, allogeneic G-NK cell therapy under current good manufacturing practices for use in clinical studies. Indapta will leverage Lonza’s process development capabilities and expertise to ensure a robust, reproducible and scalable cGMP process. [Indapta Therapeutics, Inc (Business Wire, Inc.)] Press Release

Iovance Biotherapeutics and Cellectis Enter into a Research Collaboration and Exclusive Worldwide License Agreement

Iovance Biotherapeutics, Inc. and Cellectis announced that the companies have entered into a research collaboration and exclusive worldwide license agreement whereby Iovance will license certain TALEN^® technology from Cellectis in order to develop tumor infiltrating lymphocytes that have been genetically edited to create more potent cancer therapeutics. [Cellectis] Press Release

Acepodia Announces FDA Clearance of IND for Its NK Cell Therapy Drug Candidate ACE1702 to Treat Patients with HER2-Expressing Solid Tumors

Acepodia announced it has received clearance of its Investigational New Drug (IND) application from the FDA to initiate a Phase I clinical study of its natural killer cell therapy and lead drug candidate ACE1702 in patients with HER2-expressing solid tumors. [Acepodia (Globe Newswire, Inc.)] Press Release

Precision BioSciences Announces FDA Acceptance of IND for PBCAR269A, a BCMA Targeted Genome Edited Allogeneic CAR T Therapy Candidate for Multiple Myeloma

Precision BioSciences, Inc. announced that the FDA has accepted its Investigational New Drug (IND) application for PBCAR269A, the company’s third allogeneic chimeric antigen receptor (CAR) T cell therapy candidate. The FDA has also granted Orphan Drug Designation to PBCAR269A for the treatment of multiple myeloma. [Precision BioSciences] Press Release

FDA and NIH Let Clinical Trial Sponsors Keep Results Secret, Investigation Shows

For 20 years, the US government has urged companies, universities, and other institutions that conduct clinical trials to record their results in a federal database, so doctors and patients can see whether new treatments are safe and effective. [STAT News] Editorial

Protect India’s Universities

For several weeks the world has watched as India’s citizens – including academics and students – have taken to the streets. Tens of thousands have been gathering to read out the preamble to the Indian constitution, as a mark of protest against a discriminatory new citizenship law. [Nature News] Editorial

NEW FEBS3+ Life Sciences Switzerland
February 13-14, 2020
Zurich, Switzerland

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

NEW Research Scientist – Immuno-Oncology (Ervaxx)

Postdoctoral Position – Tumor Immunology (University Hospital Carl Gustav Carus Dresden)

Chief – Division of Immunology (Boston Children’s Hospital)

Research Assistant Professor – Immunology (The University of Chicago)

Postdoctoral Fellowship – Breast Cancer Immunology and Immunotherapy (The University of Texas Southwestern Medical Center)

Postdoctoral Fellow – Immunology (University of Gothenburg)

Postdoctoral Fellow – Immune Defense and HIV (Massachusetts General Hospital)

Postdoctoral Scientist – Immunology (Karolinska Institutet)

Postdoctoral Fellow – Autoimmune Pathogenesis (Oklahoma Medical Research Foundation)

Group Leader Position – Immunology (Research Institute of Molecular Pathology)

Postdoctoral Position – Blood Cancer Immunology (University Children’s Hospital Basel)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Human Immunology News? Click here to submit!

Comments or suggestions? Submit your feedback here.