Immunology

Aging

Aging-US published this trending research paper on September 21, 2020, entitled, “Alzheimer’s disease as a systems network disorder: chronic stress/dyshomeostasis, innate immunity, and genetics” by researchers from the Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA; Buck Institute for Research on Aging, Novato, CA.

Abstract
Ineffective results of clinical trials of over 200 anti-Alzheimer's drug candidates, with a 99.6% attrition rate, suggest that the current paradigm of Alzheimer's disease (AD) may be incomplete, necessitating exploration of alternative and complementary frameworks.

Using algorithms for hypothesis independent search and expert-assisted synthesis of heterogeneous data, we attempted to reconcile multimodal clinical profiles of early-stage AD patients and accumulated research data within a parsimonious framework. Results of our analysis suggest that Alzheimer’s may not be a brain disease but a progressive system-level network disorder, which is driven by chronic network stress and dyshomeostasis. The latter can be caused by various endogenous and exogenous factors, such as chronic inflammatory conditions, infections, vascular dysfunction, head trauma, environmental toxicity, and immune disorders. Whether originating in the brain or on the periphery, chronic stress, toxicity, and inflammation are communicated to the central nervous system (CNS) via humoral and neural routes, preferentially targeting high-centrality regulatory nodes and circuits of the nervous system, and eventually manifesting as a neurodegenerative CNS disease.

In this report, we outline an alternative perspective on AD as a systems network disorder and discuss biochemical and genetic evidence suggesting the central role of chronic tissue injury/dyshomeostasis, innate immune reactivity, and inflammation in the etiopathobiology of Alzheimer’s disease.

Press release - https://www.aging-us.com/news_room/alzheimers-disease-as-a-systems-network-disorder

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DOI - https://doi.org/10.18632/aging.103883

Full text - https://www.aging-us.com/article/103883/text

Correspondence to: Alexei Kurakin email: akurakin@mednet.ucla.edu and Dale E. Bredesen email: dbredesen@mednet.ucla.edu

Keywords: Alzheimer’s disease, neurodegeneration, complex chronic disorder, network biology, systems biology

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at http://www.Aging-US.com​​ or connect with us on:

Twitter - https://twitter.com/AgingJrnl
Facebook - https://www.facebook.com/AgingUS/
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LinkedIn -  https://www.linkedin.com/company/aging​

Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com​​ or connect with @ImpactJrnls

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Trending with Impact: Treating Alzheimer’s Disease as a Systems Network Disorder

Oncotarget

Oncotarget published this trending research paper on September 28, 2021, entitled, "Multipeptide stimulated PBMCs generate TEM/TCM for adoptive cell therapy in multiple myeloma" by researchers from the Department of Immunology, Mayo Clinic, Scottsdale, AZ; Department of Biochemistry and Molecular Biology, Mayo Clinic, Scottsdale, AZ/Rochester, MN; Department of Hematology and Oncology, Mayo Clinic, Scottsdale, AZ.

Abstract:
Multiple Myeloma (MM) patients suffer disease relapse due to the development of therapeutic resistance. Increasing evidence suggests that immunotherapeutic strategies can provide durable responses. Here we evaluate the possibility of adoptive cell transfer (ACT) by generating ex vivo T cells from peripheral blood mononuclear cells (PBMCs) isolated from MM patients by employing our previously devised protocols. We designed peptides from antigens (Ags) including cancer testis antigens (CTAs) that are over expressed in MM. We exposed PBMCs from different healthy donors (HDs) to single peptides. We observed reproducible Ag-specific cluster of differentiation 4+ (CD4+) and CD8+ T cell responses on exposure of PBMCs to different single peptide sequences. These peptide sequences were used to compile four different peptide cocktails. Naïve T cells from PBMCs from MM patients or HDs recognized the cognate Ag in all four peptide cocktails, leading to generation of multiclonal Ag-specific CD4+ and CD8+ effector and central memory T (TEM and TCM, respectively) cells which produced interferon-gamma (IFN-γ), granzyme B and perforin on secondary restimulation. Furthermore, this study demonstrated that immune cells from MM patients are capable of switching metabolic programs to induce effector and memory responses. Multiple peptides and cocktails were identified that induce IFN-γ+, T1-type, metabolically active T cells, thereby paving the way for feasibility testing of ACT in phase I clinical trials.

Press release - https://www.oncotarget.com/news/pr/pbmcs-generate-tem-tcm-for-adoptive-cell-therapy-in-multiple-myeloma/

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DOI - https://doi.org/10.18632/oncotarget.28067

Full text - https://www.oncotarget.com/article/28067/text/

Correspondence to - Sandra J. Gendler - gendler.sandra@mayo.edu

Keywords - multiple myeloma, cellular therapy, CD4/CD8 T cells, peptides, immunotherapy

About Oncotarget

Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls

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Trending with Impact: New Immunotherapy Peptide Cocktail for Multiple Myeloma

Aging-US published this high-scoring research paper on November 18, 2020, entitled, “Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells: a prospective trial,” by researchers from the Research and Development Unit, Shamir Medical Center, Zerifin, Israel; The Sagol Center for Hyperbaric Medicine and Research, Shamir (Assaf-Harofeh) Medical Center, Zerifin, Israel; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Bar Ilan University, Ramat-Gan, Israel; Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel.

Abstract:
Introduction: Aging is characterized by the progressive loss of physiological capacity. At the cellular level, two key hallmarks of the aging process include telomere length (TL) shortening and cellular senescence. Repeated intermittent hyperoxic exposures, using certain hyperbaric oxygen therapy (HBOT) protocols, can induce regenerative effects which normally occur during hypoxia. The aim of the current study was to evaluate whether HBOT affects TL and senescent cell concentrations in a normal, non-pathological, aging adult population.

Methods: Thirty-five healthy independently living adults, aged 64 and older, were enrolled to receive 60 daily HBOT exposures. Whole blood samples were collected at baseline, at the 30th and 60th session, and 1-2 weeks following the last HBOT session. Peripheral blood mononuclear cells (PBMCs) telomeres length and senescence were assessed.

Results: Telomeres length of T helper, T cytotoxic, natural killer and B cells increased significantly by over 20% following HBOT. The most significant change was noticed in B cells which increased at the 30th session, 60th session and post HBOT by 25.68%±40.42 (p=0.007), 29.39%±23.39 (p=0.0001) and 37.63%±52.73 (p=0.007), respectively.

There was a significant decrease in the number of senescent T helpers by -37.30%±33.04 post-HBOT (P<0.0001). T-cytotoxic senescent cell percentages decreased significantly by -10.96%±12.59 (p=0.0004) post-HBOT.

In conclusion, the study indicates that HBOT may induce significant senolytic effects including significantly increasing telomere length and clearance of senescent cells in the aging populations.

Press release - https://www.aging-us.com/news_room/hyperbaric-oxygen-therapy-impact-on-telomere-length-immunosenescence

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DOI - https://doi.org/10.18632/aging.202188

Full text - https://www.aging-us.com/article/202188/text

Correspondence to: Amir Hadanny email: hadannya@shamir.gov.il and Shai Efrati email: efratishai@outlook.com

Keywords: telomere, senescence, aging, hyperbaric oxygen, length

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at http://www.Aging-US.com​​ or connect with us on:

Twitter - https://twitter.com/AgingJrnl​
Facebook - https://www.facebook.com/AgingUS/​
SoundCloud - https://soundcloud.com/aging-us​
YouTube - https://www.youtube.com/agingus​
LinkedIn -  https://www.linkedin.com/company/aging​

Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com​​ or connect with @ImpactJrnls

Media Contact
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Top-Performer: Hyperbaric Oxygen Therapy, Telomeres, and Immunosenescence

Teach Me in 10

In this week’s Teach Me in 10, we are joined by Dr. Sarah Rosen, a postdoctoral researcher in the Klein lab at the Washington University in St. Louis. Rosen discusses her recent efforts into discovering why the mosquito-borne West Nile Virus affects men more severely than women. She will outline why sex differences in a type of immune cell in the brain, called microglia, might underlie these different outcomes.

Why More Men Die From West Nile Virus With Dr. Sarah Rosen

Aging-US published this trending review on August 12, 2021, entitled, “Cellular senescence in lymphoid organs and immunosenescence,” by researchers from the Genetics and Genomics Graduate Program, Genetics Institute, College of Medicine, University of Florida, Gainesville, FL; Department of Neuroscience, McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL; Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL.


Abstract:
Immunosenescence is a multi-faceted phenomenon at the root of age-associated immune dysfunction. It can lead to an array of pathological conditions, including but not limited to a decreased capability to surveil and clear senescent cells (SnCs) and cancerous cells, an increased autoimmune responses leading to tissue damage, a reduced ability to tackle pathogens, and a decreased competence to illicit a robust response to vaccination. Cellular senescence is a phenomenon by which oncogene-activated, stressed or damaged cells undergo a stable cell cycle arrest. Failure to efficiently clear SnCs results in their accumulation in an organism as it ages. SnCs actively secrete a myriad of molecules, collectively called senescence-associated secretory phenotype (SASP), which are factors that cause dysfunction in the neighboring tissue. Though both cellular senescence and immunosenescence have been studied extensively and implicated in various pathologies, their relationship has not been greatly explored. In the wake of an ongoing pandemic (COVID-19) that disproportionately affects the elderly, immunosenescence as a function of age has become a topic of great importance. The goal of this review is to explore the role of cellular senescence in age-associated lymphoid organ dysfunction and immunosenescence, and provide a framework to explore therapies to rejuvenate the aged immune system.

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DOI - https://doi.org/10.18632/aging.203405

Full text - https://www.aging-us.com/article/203405/text

Correspondence to: Daohong Zhou email: zhoudaohong@cop.ufl.edu

Keywords: cellular senescence, immunosenescence, immune senescence, senescence associated secretory phenotype (SASP), thymus

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at http://www.Aging-US.com​​ or connect with us on:

Twitter - https://twitter.com/AgingJrnl​
Facebook - https://www.facebook.com/AgingUS/​
SoundCloud - https://soundcloud.com/aging-us​
YouTube - https://www.youtube.com/agingus​
LinkedIn -  https://www.linkedin.com/company/aging​

Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com​​ or connect with @ImpactJrnls

Media Contact
18009220957
MEDIA@IMPACTJOURNALS.COM

Top-Performer: Cellular Senescence in Lymphoid Organs and Immunosenescence

Creative Biolabs

Welcome to watch Creative Biolabs’ video about immune system and immune therapy. here we share some basic knowledge about T Cell Receptor Engineered T Cell Technology or TCR-T and its application on tumor therapy.
https://www.creative-biolabs.com/car-t/tcr-engineered-t-cell-development.htm

Learn about TCR Technology

Oncotarget published this trending research perspective on July 20, 2021, entitled, "Developing next generation immunomodulatory drugs and their combinations in multiple myeloma" by researchers from Bristol Myers Squibb, Summit, NJ.

Abstract:
Multiple Myeloma (MM) is an incurable malignancy with current treatment choices primarily comprising combination regimens implemented with a risk-adapted approach. Cereblon (CRBN)-targeting immunomodulatory agents (IMiDs®) lenalidomide (LEN) and pomalidomide (POM) play a central role in combination regimens due to their pleiotropic antitumor/immunomodulatory mechanisms that synergize with many anti-myeloma approved or developmental agents. Currently, more potent next generation cereblon E3 ligase modulators (CELMoDs®) - iberdomide (IBER) and CC-92480 are in clinical development. With an expanding number of active agents/therapeutic modalities and a myriad of combinatorial possibilities, physicians and drug developers share an opportunity and challenge to combine and sequence therapies to maximize long-term patient benefit. Understanding drug mechanisms and their application in combination settings as well as the unique disease biology considerations from newly diagnosed (NDMM), relapsed/refractory (RRMM), and maintenance settings will be vital to guide the development of future MM therapies centered on a backbone of IMiD or CELMoD agents. Key aspects of drug activity are critical to consider while evaluating potential combinations: direct antitumor effects, indirect antitumor cytotoxicity, immune surveillance, and adverse side effects. In addition, the treatment journey from NDMM to early and late MM relapses are connected to genomic and immune changes associated with disease progression and acquisition of resistance mechanisms. Based on the types of combinations used and the goals of therapy, insights into mechanisms of drug activity and resistance may inform treatment decisions for patients with MM. Here we focus on the evolving understanding of the molecular mechanisms of CRBN-binding drugs and how they can be differentiated and suggest a strategic framework to optimize efficacy and safety of combinations using these agents.

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DOI - https://doi.org/10.18632/oncotarget.27973

Full text - https://www.oncotarget.com/article/27973/text/
Correspondence to - Anjan Thakurta - anjan.thakurta@bms.com

Keywords - multiple myeloma, combinations, immunomodulatory agents, apoptosis, protein degradation

About Oncotarget

Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:

SoundCloud - https://soundcloud.com/oncotarget
Facebook - https://www.facebook.com/Oncotarget/
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Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls

Media Contact
MEDIA@IMPACTJOURNALS.COM
18009220957

Trending with Impact: Next Generation Immunomodulatory Drugs in Multiple Myeloma

What are viral variants? How and why do they occur? What impact can they have on our body's immune system response? These are pertinent questions right now. For this Teach Me in 10 episode, we're joined by Dr. Sean Elias from the Jenner Institute at the University of Oxford. In just 10 minutes, Dr. Elias provides you with everything you need to know about viral variants and vaccines.

Viral Variants and Vaccines With Dr. Sean Elias

Mutant library

Stable cell lines carrying a reporter gene (a tag or a fluorescent protein) cassette using CRISPR targeted genome editing via the HDR pathway is a powerful tool for monitoring endogenous target gene expression or biological processes without disrupting the target gene in vitro.

https://www.creative-biogene.com/Services/Stable-Knock-in-Cell-Line-Generation/Reporter-Genes-Knock-In-Cell-Line-Generation.html

Immunology

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