scholarly journals Smart Lipid-Based Nanosystems for Therapeutic Immune Induction against Cancers: Perspectives and Outlooks

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 26
Author(s):  
Seth-Frerich Fobian ◽  
Ziyun Cheng ◽  
Timo L. M. ten Hagen
Keyword(s):  
Cancer Immunotherapy ◽  
T Cell Receptors ◽  
Checkpoint Inhibitors ◽  
Antibody Fragments ◽  
Future Research ◽  
Drug Packaging ◽  
Immune Stimulants ◽  
Immune Capacity ◽  
Preclinical And Clinical Studies

Cancer immunotherapy, a promising and widely applied mode of oncotherapy, makes use of immune stimulants and modulators to overcome the immune dysregulation present in cancer, and leverage the host’s immune capacity to eliminate tumors. Although some success has been seen in this field, toxicity and weak immune induction remain challenges. Liposomal nanosystems, previously used as targeting agents, are increasingly functioning as immunotherapeutic vehicles, with potential for delivery of contents, immune induction, and synergistic drug packaging. These systems are tailorable, multifunctional, and smart. Liposomes may deliver various immune reagents including cytokines, specific T-cell receptors, antibody fragments, and immune checkpoint inhibitors, and also present a promising platform upon which personalized medicine approaches can be built, especially with preclinical and clinical potentials of liposomes often being frustrated by inter- and intrapatient variation. In this review, we show the potential of liposomes in cancer immunotherapy, as well as the methods for synthesis and in vivo progression thereof. Both preclinical and clinical studies are included to comprehensively illuminate prospects and challenges for future research and application.

scholarly journals Surface-Enhanced Raman Spectroscopy for Cancer Immunotherapy Applications: Opportunities, Challenges, and Current Progress in Nanomaterial Strategies

Nanomaterials ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 1145 ◽  
Author(s):  
Shuvashis Dey ◽  
Matt Trau ◽  
Kevin M. Koo
Keyword(s):  
Raman Spectroscopy ◽  
Cancer Immunotherapy ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Surface Enhanced Raman Spectroscopy ◽  
Surface Enhanced ◽  
Surface Enhanced Raman ◽  
Checkpoint Receptors

Cancer immunotherapy encompasses a variety of approaches which target or use a patient’s immune system components to eliminate cancer. Notably, the current use of immune checkpoint inhibitors to target immune checkpoint receptors such as CTLA-4 or PD-1 has led to remarkable treatment responses in a variety of cancers. To predict cancer patients’ immunotherapy responses effectively and efficiently, multiplexed immunoassays have been shown to be advantageous in sensing multiple immunomarkers of the tumor microenvironment simultaneously for patient stratification. Surface-enhanced Raman spectroscopy (SERS) is well-regarded for its capabilities in multiplexed bioassays and has been increasingly demonstrated in cancer immunotherapy applications in recent years. This review focuses on SERS-active nanomaterials in the modern literature which have shown promise for enabling cancer patient-tailored immunotherapies, including multiplexed in vitro and in vivo immunomarker sensing and imaging, as well as immunotherapy drug screening and delivery.

scholarly journals Histamine, Neuroinflammation and Neurodevelopment: A Review

2021 ◽  
Vol 15 ◽  
Author(s):  
Elliott Carthy ◽  
Tommas Ellender
Keyword(s):  
Brain Development ◽  
Neurodevelopmental Disorders ◽  
Histamine Receptor ◽  
Future Research ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Inflammatory Processes ◽  
Preclinical And Clinical Studies

The biogenic amine, histamine, has been shown to critically modulate inflammatory processes as well as the properties of neurons and synapses in the brain, and is also implicated in the emergence of neurodevelopmental disorders. Indeed, a reduction in the synthesis of this neuromodulator has been associated with the disorders Tourette’s syndrome and obsessive-compulsive disorder, with evidence that this may be through the disruption of the corticostriatal circuitry during development. Furthermore, neuroinflammation has been associated with alterations in brain development, e.g., impacting synaptic plasticity and synaptogenesis, and there are suggestions that histamine deficiency may leave the developing brain more vulnerable to proinflammatory insults. While most studies have focused on neuronal sources of histamine it remains unclear to what extent other (non-neuronal) sources of histamine, e.g., from mast cells and other sources, can impact brain development. The few studies that have started exploring this in vitro, and more limited in vivo, would indicate that non-neuronal released histamine and other preformed mediators can influence microglial-mediated neuroinflammation which can impact brain development. In this Review we will summarize the state of the field with regard to non-neuronal sources of histamine and its impact on both neuroinflammation and brain development in key neural circuits that underpin neurodevelopmental disorders. We will also discuss whether histamine receptor modulators have been efficacious in the treatment of neurodevelopmental disorders in both preclinical and clinical studies. This could represent an important area of future research as early modulation of histamine from neuronal as well as non-neuronal sources may provide novel therapeutic targets in these disorders.

scholarly journals Regulating the immunosuppressive tumor microenvironment to enhance breast cancer immunotherapy using pH-responsive hybrid membrane-coated nanoparticles

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chunai Gong ◽  
Xiaoyan Yu ◽  
Wei Zhang ◽  
Lu Han ◽  
Rong Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Immunotherapy ◽  
Checkpoint Inhibitors ◽  
Adenosine Monophosphate ◽  
Great Promise ◽  
Ph Responsive ◽  
Programmed Death ◽  
Biomimetic Membrane

AbstractThe combination of an immuno-metabolic adjuvant and immune checkpoint inhibitors holds great promise for effective suppression of tumor growth and invasion. In this study, a pH-responsive co-delivery platform was developed for metformin (Met), a known immuno-metabolic modulator, and short interfering RNA (siRNA) targeting fibrinogen-like protein 1 mRNA (siFGL1), using a hybrid biomimetic membrane (from macrophages and cancer cells)-camouflaged poly (lactic-co-glycolic acid) nanoparticles. To improve the endo-lysosomal escape of siRNA for effective cytosolic siRNA delivery, a pH-triggered CO2 gas-generating nanoplatform was developed using the guanidine group of Met. It can react reversibly with CO2 to form Met-CO2 for the pH-dependent capture/release of CO2. The introduction of Met, a conventional anti-diabetic drug, promotes programmed death-ligand 1 (PD-L1) degradation by activating adenosine monophosphate-activated protein kinase, subsequently blocking the inhibitory signals of PD-L1. As a result, siFGL1 delivery by the camouflaged nanoparticles of the hybrid biomimetic membrane can effectively silence the FGL1 gene, promoting T-cell-mediated immune responses and enhancing antitumor immunity. We found that a combination of PD-L1/programmed death 1 signaling blockade and FGL1 gene silencing exhibited high synergistic therapeutic efficacy against breast cancer in vitro and in vivo. Additionally, Met alleviated tumor hypoxia by reducing oxygen consumption and inducing M1-type differentiation of tumor-related macrophages, which improved the tumor immunosuppressive microenvironment. Our results indicate the potential of hybrid biomimetic membrane-camouflaged nanoparticles and combined Met-FGL1 blockade in breast cancer immunotherapy.

scholarly journals Phytomedicines Used for Diabetes Mellitus in Ghana: A Systematic Search and Review of Preclinical and Clinical Evidence

2019 ◽  
Vol 2019 ◽  
pp. 1-23 ◽  
Author(s):  
Michael Buenor Adinortey ◽  
Rosemary Agbeko ◽  
Daniel Boison ◽  
William Ekloh ◽  
Lydia Enyonam Kuatsienu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Medicinal Plants ◽  
Cell Function ◽  
Glucose Absorption ◽  
Mechanisms Of Action ◽  
Future Research ◽  
Secretion Inhibition ◽  
Preclinical And Clinical Studies

Background. Available data indicate that diabetes mellitus leads to elevated cost of healthcare. This imposes a huge economic burden on households, societies, and nations. As a result many Ghanaians, especially rural folks, resort to the use of phytomedicine, which is relatively less expensive. This paper aims at obtaining information on plants used in Ghana to treat diabetes mellitus, gather and present evidence-based data available to support their uses and their mechanisms of action, and identify areas for future research.Method. A catalogue of published textbooks, monographs, theses, and peer-reviewed articles of plants used in Ghanaian traditional medicine between 1987 and July 2018 for managing diabetes mellitus was obtained and used.Results. The review identified 76 plant species belonging to 45 families that are used to manage diabetes mellitus. Leaves were the part of the plants frequently used for most preparation (63.8%) and were mostly used as decoctions. Majority of the plants belonged to the Euphorbiaceae, Lamiaceae, Asteraceae, and Apocynaceae families. Pharmacological data were available on 23 species that have undergonein vitrostudies. Forty species have been studied usingin vivoanimal models. Only twelve plants and their bioactive compounds were found with data on both preclinical and clinical studies. The records further indicate that medicinal plants showing antidiabetic effects did so via biochemical mechanisms such as restitution of pancreaticβ-cell function, improvement in insulin sensitivity by receptors, stimulating rate of insulin secretion, inhibition of liver gluconeogenesis, enhanced glucose absorption, and inhibition of G-6-Pase,α-amylase, andα-glucosidase activities.Conclusion. This review contains information on medicinal plants used to manage diabetes mellitus, including their pharmacological properties and mechanisms of action as well as models used to investigate them. It also provides gaps that can form the basis for further investigations and development into useful medications for effective treatment of diabetes mellitus.

scholarly journals mRNA vaccine for cancer immunotherapy

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Lei Miao ◽  
Yu Zhang ◽  
Leaf Huang
Keyword(s):  
Cancer Immunotherapy ◽  
Cancer Vaccines ◽  
Tumor Antigens ◽  
Checkpoint Inhibitors ◽  
Rapid Development ◽  
Cost Effective ◽  
Administration Routes ◽  
Therapeutic Outcomes ◽  
Antigen Presenting

AbstractmRNA vaccines have become a promising platform for cancer immunotherapy. During vaccination, naked or vehicle loaded mRNA vaccines efficiently express tumor antigens in antigen-presenting cells (APCs), facilitate APC activation and innate/adaptive immune stimulation. mRNA cancer vaccine precedes other conventional vaccine platforms due to high potency, safe administration, rapid development potentials, and cost-effective manufacturing. However, mRNA vaccine applications have been limited by instability, innate immunogenicity, and inefficient in vivo delivery. Appropriate mRNA structure modifications (i.e., codon optimizations, nucleotide modifications, self-amplifying mRNAs, etc.) and formulation methods (i.e., lipid nanoparticles (LNPs), polymers, peptides, etc.) have been investigated to overcome these issues. Tuning the administration routes and co-delivery of multiple mRNA vaccines with other immunotherapeutic agents (e.g., checkpoint inhibitors) have further boosted the host anti-tumor immunity and increased the likelihood of tumor cell eradication. With the recent U.S. Food and Drug Administration (FDA) approvals of LNP-loaded mRNA vaccines for the prevention of COVID-19 and the promising therapeutic outcomes of mRNA cancer vaccines achieved in several clinical trials against multiple aggressive solid tumors, we envision the rapid advancing of mRNA vaccines for cancer immunotherapy in the near future. This review provides a detailed overview of the recent progress and existing challenges of mRNA cancer vaccines and future considerations of applying mRNA vaccine for cancer immunotherapies.

Specific Labeling of Protein Domains with Antibody Fragments

1981 ◽  
Vol 39 ◽  
pp. 416-417
Author(s):  
U. Aebi ◽  
L.E. Buhle ◽  
W.E. Fowler
Keyword(s):  
Image Processing ◽  
Specific Protein ◽  
Antibody Fragments ◽  
Supramolecular Organization ◽  
Two Dimensional ◽  
Ordered Structures ◽  
Virus Capsids ◽  
Processing Techniques

Many important supramolecular structures such as filaments, microtubules, virus capsids and certain membrane proteins and bacterial cell walls exist as ordered polymers or two-dimensional crystalline arrays in vivo. In several instances it has been possible to induce soluble proteins to form ordered polymers or two-dimensional crystalline arrays in vitro. In both cases a combination of electron microscopy of negatively stained specimens with analog or digital image processing techniques has proven extremely useful for elucidating the molecular and supramolecular organization of the constituent proteins. However from the reconstructed stain exclusion patterns it is often difficult to identify distinct stain excluding regions with specific protein subunits. To this end it has been demonstrated that in some cases this ambiguity can be resolved by a combination of stoichiometric labeling of the ordered structures with subunit-specific antibody fragments (e.g. Fab) and image processing of the electron micrographs recorded from labeled and unlabeled structures.

Metabolism and Distribution of Novel Tumor Targeting Drugs In Vivo

2020 ◽  
Vol 21 (13) ◽  
pp. 996-1008
Author(s):  
Mengli Wang ◽  
Qiuzheng Du ◽  
Lihua Zuo ◽  
Peng Xue ◽  
Chao Lan ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Small Molecule ◽  
High Efficiency ◽  
Tumor Therapy ◽  
Research Progress ◽  
Future Research ◽  
Pharmacokinetic Parameters ◽  
Molecular Characteristics ◽  
Targeted Drugs

Background: As a new tumor therapy, targeted therapy is becoming a hot topic due to its high efficiency and low toxicity. Drug effects of targeted tumor drugs are closely related to pharmacokinetics, so it is important to understand their distribution and metabolism in vivo. Methods: A systematic review of the literature on the metabolism and distribution of targeted drugs over the past 20 years was conducted, and the pharmacokinetic parameters of approved targeted drugs were summarized in combination with the FDA's drug instructions. Targeting drugs are divided into two categories: small molecule inhibitors and monoclonal antibodies. Novel targeting drugs and their mechanisms of action, which have been developed in recent years, are summarized. The distribution and metabolic processes of each drug in the human body are reviewed. Results: In this review, we found that the distribution and metabolism of small molecule kinase inhibitors (TKI) and monoclonal antibodies (mAb) showed different characteristics based on the differences of action mechanism and molecular characteristics. TKI absorbed rapidly (Tmax ≈ 1-4 h) and distributed in large amounts (Vd > 100 L). It was mainly oxidized and reduced by cytochrome P450 CYP3A4. However, due to the large molecular diameter, mAb was distributed to tissues slowly, and the volume of distribution was usually very low (Vd < 10 L). It was mainly hydrolyzed and metabolized into peptides and amino acids by protease hydrolysis. In addition, some of the latest drugs are still in clinical trials, and the in vivo process still needs further study. Conclusion: According to the summary of the research progress of the existing targeting drugs, it is found that they have high specificity, but there are still deficiencies in drug resistance and safety. Therefore, the development of safer and more effective targeted drugs is the future research direction. Meanwhile, this study also provides a theoretical basis for clinical accurate drug delivery.

Electromagnetic field in Alzheimer’s disease: a literature review of recent preclinical and clinical studies

2020 ◽  
Vol 17 ◽  
Author(s):  
Reem Habib Mohamad Ali Ahmad ◽  
Marc Fakhoury ◽  
Nada Lawand
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
In Vivo Studies ◽  
Key Factors ◽  
Potential Benefits ◽  
Preclinical And Clinical Studies ◽  
The Brain

: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the progressive loss of neurons leading to cognitive and memory decay. The main signs of AD include the irregular extracellular accumulation of amyloidbeta (Aβ) protein in the brain and the hyper-phosphorylation of tau protein inside neurons. Changes in Aβ expression or aggregation are considered key factors in the pathophysiology of sporadic and early-onset AD and correlate with the cognitive decline seen in patients with AD. Despite decades of research, current approaches in the treatment of AD are only symptomatic in nature and are not effective in slowing or reversing the course of the disease. Encouragingly, recent evidence revealed that exposure to electromagnetic fields (EMF) can delay the development of AD and improve memory. This review paper discusses findings from in vitro and in vivo studies that investigate the link between EMF and AD at the cellular and behavioural level, and highlights the potential benefits of EMF as an innovative approach for the treatment of AD.

scholarly journals Recent Progress in Dendritic Cell-Based Cancer Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2495
Author(s):  
Kazuhiko Matsuo ◽  
Osamu Yoshie ◽  
Kosuke Kitahata ◽  
Momo Kamei ◽  
Yuta Hara ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Immune Checkpoint ◽  
Targeted Delivery ◽  
Cancer Vaccines ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Host Immune Responses ◽  
Near Future ◽  
Identification And Characterization

Cancer immunotherapy aims to treat cancer by enhancing cancer-specific host immune responses. Recently, cancer immunotherapy has been attracting much attention because of the successful clinical application of immune checkpoint inhibitors targeting the CTLA-4 and PD-1/PD-L1 pathways. However, although highly effective in some patients, immune checkpoint inhibitors are beneficial only in a limited fraction of patients, possibly because of the lack of enough cancer-specific immune cells, especially CD8+ cytotoxic T-lymphocytes (CTLs), in the host. On the other hand, studies on cancer vaccines, especially DC-based ones, have made significant progress in recent years. In particular, the identification and characterization of cross-presenting DCs have greatly advanced the strategy for the development of effective DC-based vaccines. In this review, we first summarize the surface markers and functional properties of the five major DC subsets. We then describe new approaches to induce antigen-specific CTLs by targeted delivery of antigens to cross-presenting DCs. In this context, the chemokine receptor XCR1 and its ligand XCL1, being selectively expressed by cross-presenting DCs and mainly produced by activated CD8+ T cells, respectively, provide highly promising molecular tools for this purpose. In the near future, CTL-inducing DC-based cancer vaccines may provide a new breakthrough in cancer immunotherapy alone or in combination with immune checkpoint inhibitors.

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