scholarly journals Opportunities and Challenges in the Delivery of mRNA-Based Vaccines

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 102 ◽  
Author(s):  
Abishek Wadhwa ◽  
Anas Aljabbari ◽  
Abhijeet Lokras ◽  
Camilla Foged ◽  
Aneesh Thakur
Keyword(s):  
Infectious Disease ◽  
Immune System ◽  
Messenger Rna ◽  
Genetic Diseases ◽  
Clinical Status ◽  
Therapeutic Modality ◽  
Physiological Conditions ◽  
The Past ◽  
New Type ◽  
Cancer Immunotherapies

In the past few years, there has been increasing focus on the use of messenger RNA (mRNA) as a new therapeutic modality. Current clinical efforts encompassing mRNA-based drugs are directed toward infectious disease vaccines, cancer immunotherapies, therapeutic protein replacement therapies, and treatment of genetic diseases. However, challenges that impede the successful translation of these molecules into drugs are that (i) mRNA is a very large molecule, (ii) it is intrinsically unstable and prone to degradation by nucleases, and (iii) it activates the immune system. Although some of these challenges have been partially solved by means of chemical modification of the mRNA, intracellular delivery of mRNA still represents a major hurdle. The clinical translation of mRNA-based therapeutics requires delivery technologies that can ensure stabilization of mRNA under physiological conditions. Here, we (i) review opportunities and challenges in the delivery of mRNA-based therapeutics with a focus on non-viral delivery systems, (ii) present the clinical status of mRNA vaccines, and (iii) highlight perspectives on the future of this promising new type of medicine.

scholarly journals How Does a COVID mRNA vaccine really work?

Ubiquity ◽  
2021 ◽  
Vol 2021 (July) ◽  
pp. 1-12
Author(s):  
Walter Tichy
Keyword(s):  
Infectious Disease ◽  
Immune System ◽  
Messenger Rna ◽  
Spike Protein ◽  
Foreign Protein ◽  
The Real ◽  
Virus Rna ◽  
German Company ◽  
The Media ◽  
The U.S

The most potent weapon against COVID-19 is a vaccine based on messenger RNA (mRNA). The first of these vaccines authorized for use was developed by the German company BioNTech in cooperation with Pfizer, closely followed by the (U.S.-produced) Moderna vaccine. These vaccines send a piece of mRNA into cells of a host. The mRNA instructs the cells to produce masses of the same spike protein that also occurs on the shell of the real coronavirus. The immune system responds by learning to destroy anything showing that protein: if the real virus arrives, the immune system will attack it immediately. This much has been reported widely by the media. But important questions remain. How is mRNA actually synthesized as a transcription of the spike-producing segment of the virus' RNA? How is the selection and replication done? How does mRNA enter a host cell, and how long will it stay there? Will it produce the spike protein forever? Is it perhaps dangerous? And the biggest question of all: How does the immune system record the structure of the foreign protein, how does it recognize the invader, and how is the immune response cranked up? To answer these questions, we bring you a conversation between Ubiquity editor Walter Tichy and his daughter Dr. Evelyn Tichy, an infectious disease expert.

scholarly journals Nephrotoxicity of Cancer Immunotherapies: Past, Present and Future

2018 ◽  
Vol 29 (8) ◽  
pp. 2039-2052 ◽  
Author(s):  
Mark A. Perazella ◽  
Anushree C. Shirali
Keyword(s):  
Clinical Practice ◽  
Immune System ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Hematologic Malignancies ◽  
High Dose ◽  
Cancer Therapies ◽  
Chemotherapeutic Drugs ◽  
The Past ◽  
Cancer Immunotherapies

Nephrotoxicity from cancer therapies is common and increasingly encountered in clinical practice, such that the subfield of “onco-nephrology” has emerged. Conventional chemotherapeutic drugs and novel agents targeting specific genes/proteins are effective cancer therapies but suffer from a number of adverse kidney effects. An effective avenue of cancer treatment is immunotherapy, which uses drugs that augment immune system–mediated recognition and targeting of tumor cells. As such, leveraging the immune system to target malignant cells represents an important modality in eradicating cancer. IFN and high-dose IL-2 are older immunotherapies used in clinical practice to treat various malignancies, whereas new cancer immunotherapies have emerged over the past decade that offer even more effective treatment options. The immune checkpoint inhibitors are an exciting addition to the cancer immunotherapy armamentarium. Chimeric antigen receptor T cells are also a new immunotherapy used to treat various hematologic malignancies. However, as with the conventional and targeted cancer agents, the immunotherapies are also associated with immune-related adverse effects, which includes nephrotoxicity.

From Viral Vaccines to Messenger RNA Vaccines

2020 ◽  
Keyword(s):  
Infectious Disease ◽  
Immune System ◽  
Disease Control ◽  
Messenger Rna ◽  
Surface Protein ◽  
Infectious Agent ◽  
Smallpox Vaccine ◽  
Small Pox ◽  
Burden Of Diseases ◽  
Enormous Success

Today, the swiftness of epidemics of infectious disease is alarming. To date vaccines have been an enormous success for not only preventing but completely eradicating a number of malicious infectious disease like small pox, rubella, mumps, measles and polio as well as decreasing the burden of diseases like tetanus, measles and diphtheria etc. Vaccination has been the hallmark of disease control for hundreds of years since it was first tested by English physician Edward Jenner in 1796 and further validated by Louis Pasteur through their work on smallpox vaccine. Vaccines function by imitating an infectious agent, and by doing so, train our bodies to respond more rapidly and effectively against them. They are either a toxin or surface protein that is identical to the offending microorganism and are made from a killed or inactivated part of the pathogen. By injecting this agent our body achieves a crash course in recognizing the agent as a threat, enabling the immune system to combat the pathogen, destroy them, and lastly, protect our bodies from a future encounter.

scholarly journals Literature Review: Risk of Death in Covid-19 Patients

2020 ◽  
Vol 9 (2) ◽  
pp. 141-147
Author(s):  
Israfil Israfil ◽  
Pipit Festi Wiliyanarti ◽  
Pius Selasa
Keyword(s):  
Infectious Disease ◽  
Risk Factors ◽  
Immune System ◽  
Literature Review ◽  
Fatality Rate ◽  
Risk Of Death ◽  
Global Pandemic ◽  
The World ◽  
New Type ◽  
Treatment Facilities

Covid-19 is a contagious pulmonary infectious disease caused by a new type of coronavirus (SARS-COV-2). Covid-19 is a global pandemic that has infected millions of people and killed thousands of people in the world. Cases of death in Covid-19 patients were first discovered in China in December 2019. In Indonesia, since it was first discovered, cases of death of Covid-19 patients continue to increase and has become one of the countries with the highest fatality rate in the world reaching 9.11 percent. The purpose of this study is to determine risk factors for death in covid-19 patients in China in order to get guidance in preventing death in Covid-19 patients in Indonesia. This type of research is a literature review. The results of the study found five risk factors for death in Covid-19 patients, namely age, Covid-19 complications, the immune system (immunity), concomitant diseases (cormobidity), and treatment facilities. Suggestions of various risk factors for death in Covid-19 patients in China are expected to be a guide in efforts to prevent death in Covid-19 patients that occur in Indonesia.

scholarly journals Allogeneic Hematopoietic Transplantation for Multiple Myeloma in the New Drugs Era: A Platform to Cure

2020 ◽  
Vol 9 (11) ◽  
pp. 3437
Author(s):  
Alberto Mussetti ◽  
Maria Queralt Salas ◽  
Vittorio Montefusco
Keyword(s):  
Multiple Myeloma ◽  
Immune System ◽  
Hematopoietic Cell Transplantation ◽  
Therapeutic Potential ◽  
Clinical Status ◽  
Standard Of Care ◽  
Donor Lymphocyte Infusion ◽  
New Drugs ◽  
Post Transplant ◽  
The Past

Allogeneic hematopoietic cell transplantation (alloHCT) represents a treatment option for multiple myeloma (MM) patients. As shown in several studies, alloHCT is highly effective, but it is hampered by a high toxicity, mainly related to the graft-versus-host disease (GVHD), a complex immunological reaction ascribable to the donor’s immune system. The morbidity and mortality associated with GVHD can weaken the benefits of this procedure. On the other side, the high therapeutic potential of alloHCT is also related to the donor’s immune system, through immunological activity known as the graft-versus-myeloma effect. Clinical research over the past two decades has sought to enhance the favorable part of this balance, along with the reduction in treatment-related toxicity. Frontline alloHCT showed promising results and a potential for a cure in the past. Currently, thanks to the improved results of first-line therapies and the availability of effective second- or third-line salvage therapies, alloHCT is reserved for selected high-risk patients and is considered a clinical option. For donor lymphocyte infusion, bortezomib or lenalidomide have been used as consolidation or maintenance therapies post-transplant—none has become standard of care. For those patients who relapse, the best treatment should be evaluated considering the patient’s clinical status and the previous lines of therapy. The use of newer drugs, such as monoclonal antibodies or other immunotherapies in the post-transplant setting, deserves further investigation. However, acceptable toxicity and a synergic effect with the newer immune system could be hopefully expected.

scholarly journals Harnessing and Enhancing Macrophage Phagocytosis for Cancer Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Siqi Chen ◽  
Seigmund W. T. Lai ◽  
Christine E. Brown ◽  
Mingye Feng
Keyword(s):  
Adaptive Immunity ◽  
Therapeutic Strategy ◽  
Therapeutic Modality ◽  
Innate And Adaptive Immunity ◽  
Effective Strategies ◽  
The Past ◽  
Macrophage Phagocytosis ◽  
Effective Therapeutic Strategy ◽  
Preclinical And Clinical Studies ◽  
Cancer Immunotherapies

Cancer immunotherapy has revolutionized the paradigm for the clinical management of cancer. While FDA-approved cancer immunotherapies thus far mainly exploit the adaptive immunity for therapeutic efficacy, there is a growing appreciation for the importance of innate immunity in tumor cell surveillance and eradication. The past decade has witnessed macrophages being thrust into the spotlight as critical effectors of an innate anti-tumor response. Promising evidence from preclinical and clinical studies have established targeting macrophage phagocytosis as an effective therapeutic strategy, either alone or in combination with other therapeutic moieties. Here, we review the recent translational advances in harnessing macrophage phagocytosis as a pivotal therapeutic effort in cancer treatment. In addition, this review emphasizes phagocytosis checkpoint blockade and the use of nanoparticles as effective strategies to potentiate macrophages for phagocytosis. We also highlight chimeric antigen receptor macrophages as a next-generation therapeutic modality linking the closely intertwined innate and adaptive immunity to induce efficacious anti-tumor immune responses.

scholarly journals What Has Clinical Research in Suicide Prevention Done for You Lately?

CNS Spectrums ◽  
2006 ◽  
Vol 11 (6) ◽  
pp. 440-441 ◽  
Author(s):  
Jan Fawcett
Keyword(s):  
Suicidal Ideation ◽  
Suicide Risk ◽  
Clinical Status ◽  
Panic Attacks ◽  
Current Evidence ◽  
Suicide Risk Assessment ◽  
Short Term ◽  
The Past ◽  
Standard Risk ◽  
Suicide Plan

What have you heard or read over the past 10 years that has improved you ability to assess and manage suicide risk in your patients?There has been a paucity of data. What little data there is reviewed in this month's articles.They highlight findings that you should know about. Clinicians seem to cling to the familiar, unless some intense marketing is done.For instance, are you aware that the current evidence shows that a denial of suicide thoughts, plans, or intent—even a contract for safety—means absolutely nothing in the absence of a full suicide risk assessment?Yet clinicians seem to rely on these ’reassurances“ from their patients and are shocked when the patient later commits suicide. Why should a patient who is deciding that life is too painful to live tell you the truth? Robert I. Simon, MD, and Daniel W. Shuman, JD, review these facts.Are you aware that severe psychic anxiety, panic attacks, agitation, and severe insomnia often precede suicide within hours, days, or weeks and can be rapidly modified with treatment?On the other hand, standard risk factors for suicide such as suicidal ideation, hopelessness, and past suicidal attempts are not good predictors of suicide in the short term. A suicide plan, recent high intent attempt, or refusal to contract for safety may well indicate immediate risk, but a denial of suicidal ideation or intent and a contract for no harm mean absolutely nothing without a full suicide assessment that takes current clinical status, past suicidal tendencies, social support, and willingness to accept help into account.

scholarly journals Molecular Pathogenesis of Hodgkin Lymphoma: Past, Present, Future

2020 ◽  
Vol 21 (18) ◽  
pp. 6623 ◽  
Author(s):  
Marc Bienz ◽  
Salima Ramdani ◽  
Hans Knecht
Keyword(s):  
Immune System ◽  
Targeted Therapy ◽  
Signaling Pathways ◽  
Hodgkin Lymphoma ◽  
Genetic Instability ◽  
Host Immune System ◽  
Cellular Interactions ◽  
Classical Hodgkin Lymphoma ◽  
The Past

Our understanding of the tumorigenesis of classical Hodgkin lymphoma (cHL) and the formation of Reed–Sternberg cells (RS-cells) has evolved drastically in the last decades. More recently, a better characterization of the signaling pathways and the cellular interactions at play have paved the way for new targeted therapy in the hopes of improving outcomes. However, important gaps in knowledge remain that may hold the key for significant changes of paradigm in this lymphoma. Here, we discuss the past, present, and future of cHL, and review in detail the more recent discoveries pertaining to genetic instability, anti-apoptotic signaling pathways, the tumoral microenvironment, and host-immune system evasion in cHL.

scholarly journals Ionizable lipid nanoparticles for in utero mRNA delivery

2021 ◽  
Vol 7 (3) ◽  
pp. eaba1028
Author(s):  
Rachel S. Riley ◽  
Meghana V. Kashyap ◽  
Margaret M. Billingsley ◽  
Brandon White ◽  
Mohamad-Gabriel Alameh ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Gene Editing ◽  
Genetic Diseases ◽  
Lipid Nanoparticles ◽  
In Utero ◽  
Luciferase Mrna ◽  
Fetal Size ◽  
Mouse Fetuses ◽  
Clinical Advances ◽  
Immature Immune System

Clinical advances enable the prenatal diagnosis of genetic diseases that are candidates for gene and enzyme therapies such as messenger RNA (mRNA)–mediated protein replacement. Prenatal mRNA therapies can treat disease before the onset of irreversible pathology with high therapeutic efficacy and safety due to the small fetal size, immature immune system, and abundance of progenitor cells. However, the development of nonviral platforms for prenatal delivery is nascent. We developed a library of ionizable lipid nanoparticles (LNPs) for in utero mRNA delivery to mouse fetuses. We screened LNPs for luciferase mRNA delivery and identified formulations that accumulate within fetal livers, lungs, and intestines with higher efficiency and safety compared to benchmark delivery systems, DLin-MC3-DMA and jetPEI. We demonstrate that LNPs can deliver mRNAs to induce hepatic production of therapeutic secreted proteins. These LNPs may provide a platform for in utero mRNA delivery for protein replacement and gene editing.

scholarly journals Mesenchymal stem cells and oncolytic viruses: joining forces against cancer

2021 ◽  
Vol 9 (2) ◽  
pp. e001684
Author(s):  
Rafael Moreno
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Immune System ◽  
Oncolytic Viruses ◽  
Immunogenic Cell Death ◽  
The Past ◽  
Physical Barriers ◽  
Immunogenic Properties ◽  
New Strategies

The development of oncolytic viruses (OVs) has increased significantly in the past 20 years, with many candidates entering clinical trials and three of them receiving approval for some indications. Recently, OVs have also gathered interest as candidates to use in combination with immunotherapies for cancer due to their immunogenic properties, which include immunogenic cell death and the possibility to carry therapeutic transgenes in their genomes. OVs transform non-immunogenic ‘cold’ tumors into inflamed immunogenic ‘hot’ tumors, where immunotherapies show the highest efficacy. However, in monotherapy or in combination with immunotherapy, OVs face numerous challenges that limit their successful application, in particular upon systemic administration, such as liver sequestration, neutralizing interactions in blood, physical barriers to infection, and fast clearance by the immune system. In this regard, the use of mesenchymal stem cells (MSCs) as cells carrier for OV delivery addresses many of these obstacles acting as virus carriers and factories, expressing additional transgenes, and modulating the immune system. Here, I review the current progress of OVs-loaded MSCs in cancer, focusing on their interaction with the immune system, and discuss new strategies to improve their therapeutic efficacy.

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