scholarly journals PD-L1 as a Potential Target in Cancer Therapy (Review)

2021 ◽  
Vol 10 (1) ◽  
pp. 31-36
Author(s):  
N. N. Andrusova ◽  
M. A. Kolganova ◽  
A. V. Aleshina ◽  
I. E. Shohin
Keyword(s):  
Clinical Trials ◽  
Immune System ◽  
Cancer Treatment ◽  
Death Receptor ◽  
Effective Response ◽  
Vast Number ◽  
Mediated Effects ◽  
Immune Mediated ◽  
Oncological Diseases ◽  
High Level

Introduction. Cancer is one of the most serious and common diseases with a high level of mortality. Due to this reason the searching of new directions and methods of cancer treatment is becoming more and more important with each passing year. Significant advances in cancer immunotherapy have been reached over the past few decades. Moreover, an inhibition of the interaction between the programmed cell death receptor (PD-1) and its ligand (PD-L1), is sure to be perspective direction of the immuno-oncological therapy development.Text. PD-1/PD-L1 interaction plays a pivotal role in negative regulation of immune system, that protects host’s cells and tissues from the excessive immune response. However, it is also used by tumor cells to avoid the host's immune system. The discovery of this mechanism led to the development of inhibiting PD-1 or PD-L1 agents that enhance anti-tumor immunity. Meanwhile, anti-PD-L1 agents provide less toxicity in comparison with anti-PD-1 agents. FDA currently approved Atesolizumab, Durvalumab, and Avelumab PD-L1 inhibitors for cancer treatment. These agents demonstrated effective response during the clinical trials, however, they are used for a limited number of oncological diseases. In addition, BMS-936559 is a promising agent that had passed the first stage of the clinical trials. Nevertheless, immunotherapy involving PD-L1 inhibitors is closely related to a vast number of severe side effects including immune-mediated effects caused by the inhibition of PD-L1 ligands located on healthy cells. In these terms, the development of new agents deprived of these disadvantages is the reason for further studies.Conclusion. Immunotherapy in cancer uncovers new perspectives in treatment of refractory to standard therapies forms of cancer. And the development of new and improvement of existing PD-L1 blocking agents are of great importance in fighting against tumoral diseases.

Vaccine Ingredients: Components that Influence Vaccine Efficacy

2017 ◽  
Vol 17 (5) ◽  
pp. 451-466 ◽  
Author(s):  
Aneta Kocourkova ◽  
Jan Honegr ◽  
Kamil Kuca ◽  
Jana Danova
Keyword(s):  
Clinical Trials ◽  
Immune System ◽  
Adaptive Immunity ◽  
Active Ingredient ◽  
Vaccine Efficacy ◽  
Vast Number ◽  
Wide Range ◽  
Other Substances ◽  
Antigenic Material

Vaccination is defined as the administration of an antigenic material in order to stimulate the immune system, leading to the development of adaptive immunity to a pathogen. Vaccines can prevent or reduce morbidity from a vast number of infections. This manuscript presents an analysis of vaccine types and vaccine substances, concentrating on individual components including the active ingredient, adjuvants, preservatives, stabilizers, inactivators, antibiotics, diluents and other substances. While many papers have been published on individual vaccine components, this review provides detail on a wide range of the most commonly-used vaccine ingredients and components that have been tested in clinical trials.

scholarly journals Immunotherapies: Exploiting the Immune System for Cancer Treatment

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Jeffrey Koury ◽  
Mariana Lucero ◽  
Caleb Cato ◽  
Lawrence Chang ◽  
Joseph Geiger ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Immune System ◽  
T Cell ◽  
Cancer Treatment ◽  
Checkpoint Inhibitors ◽  
Cell Transfer ◽  
Adoptive T Cell Transfer ◽  
Ancient Egyptian ◽  
Biological Therapeutics ◽  
T Cell Transfer

Cancer is a condition that has plagued humanity for thousands of years, with the first depictions dating back to ancient Egyptian times. However, not until recent decades have biological therapeutics been developed and refined enough to safely and effectively combat cancer. Three unique immunotherapies have gained traction in recent decades: adoptive T cell transfer, checkpoint inhibitors, and bivalent antibodies. Each has led to clinically approved therapies, as well as to therapies in preclinical and ongoing clinical trials. In this review, we outline the method by which these 3 immunotherapies function as well as any major immunotherapeutic drugs developed for treating a variety of cancers.

scholarly journals Hogyan ellenőrzi az immunrendszer a daganatok kialakulásának és növekedésének folyamatát?

2016 ◽  
Vol 157 (Supplement 2) ◽  
pp. 3-8
Author(s):  
Gábor Sütő
Keyword(s):  
Immune System ◽  
Biological Network ◽  
Antiinflammatory Activity ◽  
Inflammatory Diseases ◽  
Living Organism ◽  
Effective Response ◽  
The Past ◽  
Oncological Diseases ◽  
Recent Developments

The role of immune system is the maintenace of the integritiy of the living organism. The elements of the immune system are connected by several ways forming a complex biological network. This network senses the changes of the inner and outer environment and works out the most effective response against infections and tumors. Dysfunction of the immune system leads to the development of cancer development and chronic inflammatory diseases. Modulation of the checkpoints of the immune system opened new perspecitves in the treatment of rheumatological and oncological diseases as well. Beside the potent antiinflammatory activity, new therapies are able to stimulate anticancer activity of the immune system. The result of these recent developments is a better outcome of malignant diseases, which had an unfavorable outcome in the past. Orv. Hetil., 2016, 157(Suppl. 2), 3–8.

DMXAA (Vadimezan, ASA404) is a multi-kinase inhibitor targeting VEGFR2 in particular

2012 ◽  
Vol 122 (10) ◽  
pp. 449-465 ◽  
Author(s):  
Christina M. Buchanan ◽  
Jen-Hsing Shih ◽  
Jonathan W. Astin ◽  
Gordon W. Rewcastle ◽  
Jack U. Flanagan ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Acetic Acid ◽  
Kinase Inhibitor ◽  
Umbilical Vein ◽  
Growth Factor Receptor ◽  
Phase Iii ◽  
Tumour Regression ◽  
Inhibitory Effects ◽  
Mediated Effects ◽  
Immune Mediated

The flavone acetic acid derivative DMXAA [5,6-dimethylXAA (xanthenone-4-acetic acid), Vadimezan, ASA404] is a drug that displayed vascular-disrupting activity and induced haemorrhagic necrosis and tumour regression in pre-clinical animal models. Both immune-mediated and non-immune-mediated effects contributed to the tumour regression. The vascular disruption was less in human tumours, with immune-mediated effects being less prominent, but nonetheless DMXAA showed promising effects in Phase II clinical trials in non-small-cell lung cancer. However, these effects were not replicated in Phase III clinical trials. It has been difficult to understand the differences between the pre-clinical findings and the later clinical trials as the molecular targets for the agent have never been clearly established. To investigate the mechanism of action, we sought to determine whether DMXAA might target protein kinases. We found that, at concentrations achieved in blood during clinical trials, DMXAA has inhibitory effects against several kinases, with most potent effects being on members of the VEGFR (vascular endothelial growth factor receptor) tyrosine kinase family. Some analogues of DMXAA were even more effective inhibitors of these kinases, in particular 2-MeXAA (2-methylXAA) and 6-MeXAA (6-methylXAA). The inhibitory effects were greatest against VEGFR2 and, consistent with this, we found that DMXAA, 2-MeXAA and 6-MeXAA were able to block angiogenesis in zebrafish embryos and also inhibit VEGFR2 signalling in HUVECs (human umbilical vein endothelial cells). Taken together, these results indicate that at least part of the effects of DMXAA are due to it acting as a multi-kinase inhibitor and that the anti-VEGFR activity in particular may contribute to the non-immune-mediated effects of DMXAA on the vasculature.

Evaluation of Associated Genes with Traumatic Pain: A Systematic Review

2021 ◽  
Vol 20 ◽  
Author(s):  
Hamid Reza Rasouli ◽  
Samira Talebi ◽  
Fathollah Ahmadpour
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Immune System ◽  
Signaling Pathway ◽  
Neural Development ◽  
Metabolic Pathways ◽  
Spinal Cord Injuries ◽  
Death Receptor ◽  
Cochrane Library ◽  
Molecular Pathways

Objectives: The knowledge about molecular pathway of traumatic pain relief is less documented. The systematic review study aimed to identify the genes and molecular pathways associated to various traumatic pain. Methods: The online databases such as EMBASE, MEDLINE, PubMed, Cochrane Library, International Clinical Trials Registry Platform, and Clinical Trials, Google Scholar, Wiley, ISI Web of Knowledge, and Scopus were searched. Two review authors separately searched and screened the titles and abstracts of all records, and the third expert reviewer author resolved disagreement of them. Information regarding study’s design, various trauma injuries, types of genes, and the molecular pathways were recorded. The data about genes and molecular pathways obtained via GeneCards®: The Human Gene Database (https://www.genecards.org). Results: Studies about trauma injuries types regarding nerve and Spinal Cord Injuries (SCIs) (12 records), Hypertrophic scar with Severe Pain (one record), severe post-traumatic musculoskeletal pain (MSP) (one record), and orthopedic trauma (one record) were included. The main molecular pathways including immune system, apoptosis, and death receptor signaling, T-cell antigen receptor (TCR) signaling pathway, oxidative stress, interleukin(s) mediated signaling pathway, biological oxidations, metabolic pathways (especially amino acid metabolism and amino group), focal adhesion, the proliferation of vascular, epithelial, and connective tissue cells, angiogenesis and neural development were identified. Conclusion: The immune system, apoptosis, and metabolic pathways are crucial for understanding the roles of genes in traumatic pain. It is recommended that these identified pathways and related genes can be a therapeutically target for pain management in trauma injuries patients. Also, pathways and related genes should be considered discriminately regarding various types of trauma injuries.

New Trends in Anti-Cancer Therapy: Combining Conventional Chemotherapeutics with Novel Immunomodulators

2018 ◽  
Vol 25 (36) ◽  
pp. 4758-4784 ◽  
Author(s):  
Amy L. Wilson ◽  
Magdalena Plebanski ◽  
Andrew N. Stephens
Keyword(s):  
Clinical Trials ◽  
Cell Death ◽  
Immune System ◽  
Cancer Therapy ◽  
Immune Cell ◽  
Cytotoxic T Lymphocyte ◽  
Tumour Microenvironment ◽  
Immune Checkpoints ◽  
Tumour Regression ◽  
Cell Trafficking

Cancer is one of the leading causes of death worldwide, and current research has focused on the discovery of novel approaches to effectively treat this disease. Recently, a considerable number of clinical trials have demonstrated the success of immunomodulatory therapies for the treatment of cancer. Monoclonal antibodies can target components of the immune system to either i) agonise co-stimulatory molecules, such as CD137, OX40 and CD40; or ii) inhibit immune checkpoints, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death-1 (PD-1) and its corresponding ligand PD-L1. Although tumour regression is the outcome for some patients following immunotherapy, many patients still do not respond. Furthermore, chemotherapy has been the standard of care for most cancers, but the immunomodulatory capacity of these drugs has only recently been uncovered. The ability of chemotherapy to modulate the immune system through a variety of mechanisms, including immunogenic cell death (ICD), increased antigen presentation and depletion of regulatory immune cells, highlights the potential for synergism between conventional chemotherapy and novel immunotherapy. In addition, recent pre-clinical trials indicate dipeptidyl peptidase (DPP) enzyme inhibition, an enzyme that can regulate immune cell trafficking to the tumour microenvironment, as a novel cancer therapy. The present review focuses on the current immunological approaches for the treatment of cancer, and summarizes clinical trials in the field of immunotherapy as a single treatment and in combination with chemotherapy.

The Immune System Regulation in Sepsis: From Innate to Adaptive

2019 ◽  
Vol 20 (8) ◽  
pp. 799-816 ◽  
Author(s):  
Yue Qiu ◽  
Guo-wei Tu ◽  
Min-jie Ju ◽  
Cheng Yang ◽  
Zhe Luo
Keyword(s):  
Clinical Trials ◽  
Immune System ◽  
Systemic Inflammatory Response Syndrome ◽  
Inflammatory Response ◽  
Immune Cells ◽  
Current Knowledge ◽  
Systemic Inflammatory Response ◽  
Immune System Regulation

Sepsis, which is a highly heterogeneous syndrome, can result in death as a consequence of a systemic inflammatory response syndrome. The activation and regulation of the immune system play a key role in the initiation, development and prognosis of sepsis. Due to the different periods of sepsis when the objects investigated were incorporated, clinical trials often exhibit negative or even contrary results. Thus, in this review we aim to sort out the current knowledge in how immune cells play a role during sepsis.

scholarly journals Oncolytic Virotherapy Treatment of Breast Cancer: Barriers and Recent Advances

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1128
Author(s):  
Amy Kwan ◽  
Natalie Winder ◽  
Munitta Muthana
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Cell Death ◽  
Immune System ◽  
Menopausal Status ◽  
Oncolytic Virotherapy ◽  
Immunogenic Cell Death ◽  
Tumour Type ◽  
Common Cancer ◽  
Direct Cell

Oncolytic virotherapy (OV) is an emerging class of immunotherapeutic drugs. Their mechanism of action is two-fold: direct cell lysis and unmasking of the cancer through immunogenic cell death, which allows the immune system to recognize and eradicate tumours. Breast cancer is the most common cancer in women and is challenging to treat with immunotherapy modalities because it is classically an immunogenically “cold” tumour type. This provides an attractive niche for OV, given viruses have been shown to turn “cold” tumours “hot,” thereby opening a plethora of treatment opportunities. There has been a number of pre-clinical attempts to explore the use of OV in breast cancer; however, these have not led to any meaningful clinical trials. This review considers both the potential and the barriers to OV in breast cancer, namely, the limitations of monotherapy and the scope for combination therapy, improving viral delivery and challenges specific to the breast cancer population (e.g., tumour subtype, menopausal status, age).

scholarly journals A Roadmap to Inform Development, Validation and Approval of Digital Mobility Outcomes: The Mobilise-D Approach

2020 ◽  
Vol 4 (1) ◽  
pp. 13-27 ◽  
Author(s):  
Lynn Rochester ◽  
Claudia Mazzà ◽  
Arne Mueller ◽  
Brian Caulfield ◽  
Marie McCarthy ◽  
...  
Keyword(s):  
Health Care ◽  
Clinical Trials ◽  
Health Care Professionals ◽  
Digital Health ◽  
Disease Status ◽  
Proximal Femoral Fracture ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Physical Mobility ◽  
High Level

Health care has had to adapt rapidly to COVID-19, and this in turn has highlighted a pressing need for tools to facilitate remote visits and monitoring. Digital health technology, including body-worn devices, offers a solution using digital outcomes to measure and monitor disease status and provide outcomes meaningful to both patients and health care professionals. Remote monitoring of physical mobility is a prime example, because mobility is among the most advanced modalities that can be assessed digitally and remotely. Loss of mobility is also an important feature of many health conditions, providing a read-out of health as well as a target for intervention. Real-world, continuous digital measures of mobility (digital mobility outcomes or DMOs) provide an opportunity for novel insights into health care conditions complementing existing mobility measures. Accepted and approved DMOs are not yet widely available. The need for large collaborative efforts to tackle the critical steps to adoption is widely recognised. Mobilise-D is an example. It is a multidisciplinary consortium of 34 institutions from academia and industry funded through the European Innovative Medicines Initiative 2 Joint Undertaking. Members of Mobilise-D are collaborating to address the critical steps for DMOs to be adopted in clinical trials and ultimately health care. To achieve this, the consortium has developed a roadmap to inform the development, validation and approval of DMOs in Parkinson’s disease, multiple sclerosis, chronic obstructive pulmonary disease and recovery from proximal femoral fracture. Here we aim to describe the proposed approach and provide a high-level view of the ongoing and planned work of the Mobilise-D consortium. Ultimately, Mobilise-D aims to stimulate widespread adoption of DMOs through the provision of device agnostic software, standards and robust validation in order to bring digital outcomes from concept to use in clinical trials and health care.

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