scholarly journals Cancer Therapy Targeting CD47/SIRPα

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6229
Author(s):  
Nazli Dizman ◽  
Elizabeth I. Buchbinder
Keyword(s):  
Immune Responses ◽  
Clinical Evidence ◽  
Immune Escape ◽  
Cell Surface Molecule ◽  
Adaptive Immune ◽  
The Past ◽  
A Cell ◽  
Cancer Types ◽  
Early Phase Clinical Trials ◽  
Immune Checkpoint Blockers

In the past decade, the field of cancer immunotherapy has rapidly advanced, establishing a crucial role for immune checkpoint blockers in the treatment of a variety of cancer types. In parallel with these remarkable clinical developments, further efforts have focused on ways of unleashing adaptive immune responses against cancer. CD47, a cell surface molecule overexpressed by several cancer types that facilitates immune escape from macrophages, dendritic cells and natural killer cells, and its ligand SIRPα, have emerged as potential therapeutic targets. A number of agents directed to CD47/SIRPα have been developed and demonstrated preclinical activity. Early phase clinical trials are investigating CD47/SIRPα directed agents with available data, suggesting safety and preliminary activity. Herein, we provide an overview of the mechanistic rationale of targeting CD47/SIRPα axis and associated clinical evidence.

scholarly journals SARS-CoV-2 Serology Status Detected by Commercialized Platforms Distinguishes Previous Infection and Vaccination Adaptive Immune Responses

2021 ◽  
Author(s):  
Raymond T. Suhandynata ◽  
Nicholas J. Bevins ◽  
Jenny T. Tran ◽  
Deli Huang ◽  
Melissa A. Hoffman ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Adaptive Immune Response ◽  
Antibody Assay ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Previous Infection ◽  
A Cell

AbstractBackgroundThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected over 110 million individuals and led to 2.5 million deaths worldwide. As more individuals are vaccinated, the clinical performance and utility of SARS-CoV-2 serology platforms needs to be evaluated.MethodsThe ability of four commercial SARS-CoV-2 serology platforms to detect previous infection or vaccination were evaluated using a cohort of 53 SARS-CoV-2 PCR-positive patients, 89 SARS-CoV-2-vaccinated healthcare workers (Pfizer or Moderna), and 127 SARS-CoV-2 negative patients. Serology results were compared to a cell based SARS-CoV-2 pseudovirus (PSV) neutralizing antibodies assay.ResultsThe Roche S-(spike) antibody and Diazyme neutralizing antibodies (NAbs) assays detected adaptive immune response in 100.0% and 90.1% of vaccinated individuals who received two-doses of vaccine (initial and booster), respectively. The Roche N-(nucleocapsid) antibody assay and Diazyme IgG assay did not detect adaptive immune response in vaccinated individuals. The Diazyme Nabs assay correlated with the PSV SARS-CoV-2 ID50 neutralization titers (R2= 0.70), while correlation of the Roche S-antibody assay was weaker (R2= 0.39). Median PSV SARS-CoV-2 ID50 titers more than doubled in vaccinated individuals who received two-doses of the Moderna vaccine (ID50: 597) compared to individuals that received a single dose (ID50: 284).ConclusionsThe Roche S-antibody and Diazyme NAbs assays robustly detected adaptive immune responses in SARS-CoV-2 vaccinated individuals and SARS-CoV-2 infected individuals. The Diazyme NAbs assay strongly correlates with the PSV SARS-CoV-2 NAbs in vaccinated individuals. Understanding the reactivity of commercially available serology platforms is important when distinguishing vaccination response versus natural infection.SummaryThe Roche S (spike protein)-antibody and Diazyme neutralizing-antibodies (NAbs) assays were evaluated for their clinical utility in the detection of SARS-CoV-2 related adaptive immune responses by testing SARS-CoV-2 PCR-confirmed patients, SARS-CoV-2-vaccinated individuals, and SARS-CoV-2-negative individuals. Commercial serology results were compared to results generated using a cell-based SARS-CoV-2 pseudovirus (PSV) NAbs assay and previously validated SARS-CoV-2 commercial serology assays (Roche N (nucleocapsid protein) antibody and Diazyme IgG). We demonstrate that the Roche S-antibody and Diazyme NAbs assays detected adaptive immune response in SARS-CoV-2 vaccinated individuals and the presence of SARS-CoV-2 PSV NAbs. The Roche S-antibody assay had an observed positive percent agreement (PPA) of 100% for individuals who received two doses of the Pfizer or Moderna vaccine. By contrast, the Roche N assay and Diazyme IgG assay did not detect vaccine adaptive immune responses. Our findings also indicate that the Diazyme NAbs assay correlates strongly with the levels of SARS-CoV-2 ID50 neutralization titers using the PSV Nab assay in vaccinated individuals.

scholarly journals Prior Exposure to Coxsackievirus A21 Does Not Mitigate Oncolytic Therapeutic Efficacy

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4462
Author(s):  
William J. Burnett ◽  
David M. Burnett ◽  
Gennie Parkman ◽  
Andrew Ramstead ◽  
Nico Contreras ◽  
...  
Keyword(s):  
Immune Responses ◽  
Therapeutic Efficacy ◽  
Oncolytic Viruses ◽  
Prior Exposure ◽  
Adaptive Immune Responses ◽  
Critical Determinant ◽  
Adaptive Immune ◽  
Coxsackievirus A21 ◽  
Selection For ◽  
Early Phase Clinical Trials

Oncolytic viruses (OVs) are being developed as a type of immunotherapy and have demonstrated durable tumor responses and clinical efficacy. One such OV, Coxsackievirus A21 (CVA21), exhibited therapeutic efficacy in early phase clinical trials, demonstrating the ability to infect and kill cancer cells and stimulate anti-tumor immune responses. However, one of the major concerns in using this common cold virus as a therapeutic is the potential for innate and adaptive immune responses to mitigate the benefits of viral infection, particularly in individuals that have been exposed to coxsackievirus prior to treatment. In this study, we assess melanoma responses to CVA21 in the absence or presence of prior exposure to the virus. Melanomas were transplanted into naïve or CVA21-immunized C57BL6 mice and the mice were treated with intratumoral (IT) CVA21. We find that prior exposure to CVA21 does not dramatically affect tumor responses, nor does it alter overall survival. Our results suggest that prior exposure to coxsackievirus is not a critical determinant of patient selection for IT CVA21 interventions.

scholarly journals MiR-146a in Immunity and Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Nicole Rusca ◽  
Silvia Monticelli
Keyword(s):  
Immune Responses ◽  
Recent Progress ◽  
Viral Infections ◽  
Cellular Functions ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Different Types ◽  
A Cell ◽  
And Function

MicroRNAs (miRNAs) are regulatory molecules able to influence all aspects of the biology of a cell. They have been associated with diseases such as cancer, viral infections, and autoimmune diseases, and in recent years, they also emerged as important regulators of immune responses. MiR-146a in particular is rapidly gaining importance as a modulator of differentiation and function of cells of the innate as well as adaptive immunity. Given its importance in regulating key cellular functions, it is not surprising that miR-146a expression was also found dysregulated in different types of tumors. In this paper, we summarize recent progress in understanding the role of miR-146a in innate and adaptive immune responses, as well as in disease.

scholarly journals The Role of Creatine in the Development and Activation of Immune Responses

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 751
Author(s):  
Eric C. Bredahl ◽  
Joan M. Eckerson ◽  
Steven M. Tracy ◽  
Thomas L. McDonald ◽  
Kristen M. Drescher
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Health Care Professionals ◽  
Elite Athletes ◽  
Nutritional Supplements ◽  
The Elderly ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
The Past

The use of dietary supplements has become increasingly common over the past 20 years. Whereas supplements were formerly used mainly by elite athletes, age and fitness status no longer dictates who uses these substances. Indeed, many nutritional supplements are recommended by health care professionals to their patients. Creatine (CR) is a widely used dietary supplement that has been well-studied for its effects on performance and health. CR also aids in recovery from strenuous bouts of exercise by reducing inflammation. Although CR is considered to be very safe in recommended doses, a caveat is that a preponderance of the studies have focused upon young athletic individuals; thus there is limited knowledge regarding the effects of CR on children or the elderly. In this review, we examine the potential of CR to impact the host outside of the musculoskeletal system, specifically, the immune system, and discuss the available data demonstrating that CR can impact both innate and adaptive immune responses, together with how the effects on the immune system might be exploited to enhance human health.

scholarly journals Receptor Tyrosine Kinases as Candidate Prognostic Biomarkers in Meningioma

2021 ◽  
Author(s):  
Rafael Roesler ◽  
Barbara Kunzler Souza ◽  
Gustavo R. Isolan
Keyword(s):  
Tyrosine Kinases ◽  
Clinical Evidence ◽  
Growth Factor Receptor ◽  
Prognostic Biomarkers ◽  
Clinical Prognosis ◽  
Erbb Family ◽  
The Past ◽  
Cancer Types ◽  
Epidermal Growth

Meningioma (MGM) is the most common type of intracranial tumor in adults. The validation of novel prognostic biomarkers to better inform tumor stratification and clinical prognosis is urgently needed. Many molecular and cellular alterations have been described in MGM tumors over the past few years, providing a rational basis for the identification of biomarkers and therapeutic targets. The role of receptor tyrosine kinase (RTKs), including those of the ErbB family of receptors, as oncogenes has been well established in several cancer types. Here, we review histological, molecular, and clinical evidence suggesting that RTKs, including the epidermal growth factor receptor (EGFR, ErbB 1), as well as other members of the ErbB family, may be useful as biomarkers in MGM.

scholarly journals Serum IL-33 as a biomarker in different diseases: useful parameter or much need for clarification?

2021 ◽  
Vol 10 ◽  
pp. 20-25
Author(s):  
Stefan Erfurt ◽  
Meike Hoffmeister ◽  
Stefanie Oess ◽  
Katharina Asmus ◽  
Oliver Ritter ◽  
...  
Keyword(s):  
Immune Responses ◽  
Potential Role ◽  
Kidney Injury ◽  
Diverse Range ◽  
Interleukin 33 ◽  
Adaptive Immune ◽  
The Past ◽  
Predictive Role ◽  
Adipose Tissue Cells

Interleukin-33 (IL-33), a member of the IL-1 family, is critically involved in the modulation of the activity of a diverse range of immunocompetent cells. Essential roles have been implicated in cardioprotection, in both innate and adaptive immune responses in mucosal organs, and in the maintenance of adipose tissue cells. Over the past 10 years, several studies evaluated the usability of IL-33 as a biomarker in diseases of inflammatory and noninflammatory origin. Our group is currently evaluating the predictive role of serum IL-33 in acute kidney injury (AKI). The aim of the article is to discuss selected studies on IL-33 in different diseases and its potential role as a biomarker molecule.

scholarly journals IL-27 regulation of innate immunity and control of microbial growth

2020 ◽  
Vol 6 (7) ◽  
pp. FSO588
Author(s):  
Jessica M Povroznik ◽  
Cory M Robinson
Keyword(s):  
Immune Responses ◽  
Microbial Growth ◽  
Innate Immune ◽  
Inflammatory Cytokine Production ◽  
Adaptive Immune ◽  
A Cell ◽  
Th2 Immunity ◽  
Context Specific ◽  
Opposing Effects ◽  
And Control

IL-27 is a pleiotropic cytokine capable of influencing both innate and adaptive immune responses. With anti- and pro-inflammatory activity, IL-27 exerts its opposing effects in a cell-dependent and infectious context-specific manner. Upon pathogenic stimuli, IL-27 regulates innate immune cells, such as monocytes, dendritic cells, macrophages and neutrophils. Immune responses involving these innate cells that are negatively regulated by IL-27 signaling include inflammatory cytokine production, phagolysosomal acidification following phagocytosis, oxidative burst and autophagy. IL-27 signaling is crucial in maintaining the subtle balance between Th1 and Th2 immunity, in which protective inflammation is upregulated within the early stages of infection and subsequently downregulated once microbial growth is controlled. The immunomodulatory effects of IL-27 provide promising therapeutic targets for multiple disease types.

scholarly journals Peptidoglycan-linked protein A promotes T cell-dependent antibody expansion duringStaphylococcus aureusinfection

2016 ◽  
Vol 113 (20) ◽  
pp. 5718-5723 ◽  
Author(s):  
Hwan Keun Kim ◽  
Fabiana Falugi ◽  
Dominique M. Missiakas ◽  
Olaf Schneewind
Keyword(s):  
Immune Responses ◽  
Tandem Repeats ◽  
Protein A ◽  
B Cell Receptors ◽  
Staphylococcal Protein A ◽  
Heavy Chains ◽  
Persistent Infections ◽  
Adaptive Immune ◽  
Binding Domains ◽  
A Cell

A hallmark ofStaphylococcus aureusdisease in humans is persistent infections without development of protective immune responses. Infected patients generate VH3 plasmablast expansions and increased VH3 idiotype Ig; however, the mechanisms for staphylococcal modification of immune responses are not known. We report here thatS. aureus-infected mice generate VH3 antibody expansions via a mechanism requiring MHC-restricted antigen presentation to CD4+T cells and staphylococcal protein A (SpA), a cell wall-anchored surface molecule that binds Fcγ and VH3 variant heavy chains of Ig. VH3 expansion occurred with peptidoglycan-linked SpA from the bacterial envelope but not with recombinant SpA, and optimally required five tandem repeats of its Ig-binding domains. Signaling via receptor-interacting serine/threonine protein kinase 2 (RIPK2) was essential for implementing peptidoglycan-linked SpA superantigen activity. VH3 clan IgG fromS. aureus-infected or SpA-treated animals was not pathogen-specific, suggesting that SpA cross-linking of VH3 idiotype B-cell receptors and activation via attached peptidoglycan are the determinants of staphylococcal escape from adaptive immune responses.

Dendritic Cells as Arbiters of Peritoneal Immune Responses

2006 ◽  
Vol 26 (1) ◽  
pp. 8-25 ◽  
Author(s):  
Michelle L. McCully ◽  
Joaquín Madrenas
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Adaptive Immune Response ◽  
Immune Defense ◽  
Dendritic Cell Differentiation ◽  
Adaptive Immune ◽  
The Past ◽  
Key Players ◽  
And Function

During the past few years, there has been a substantial increase in the understanding of innate immunity. Dendritic cells are emerging as key players in the orchestration of this early phase of immune responses, with a role that will translate into the subsequent type of adaptive immune response against infection. Here we provide an overview of dendritic cell differentiation and function, with particular emphasis on those features unique to the immune defense of the peritoneal cavity and in the context of peritoneal dialysis-associated immune responses. The reader is referred to the primary references included in the accompanying list for specific details in this fascinating field.

Monocytes in the Tumor Microenvironment

2021 ◽  
Vol 16 (1) ◽  
pp. 93-122
Author(s):  
Stefano Ugel ◽  
Stefania Canè ◽  
Francesco De Sanctis ◽  
Vincenzo Bronte
Keyword(s):  
Tumor Microenvironment ◽  
Immune Responses ◽  
Tumor Cells ◽  
Current Knowledge ◽  
Tumor Development ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
The Past ◽  
Immunosuppressive Tumor Microenvironment ◽  
Antigen Presenting

Immunotherapy has revolutionized cancer treatment over the past decade. Nonetheless, prolonged survival is limited to relatively few patients. Cancers enforce a multifaceted immune-suppressive network whose nature is progressively shaped by systemic and local cues during tumor development. Monocytes bridge innate and adaptive immune responses and can affect the tumor microenvironment through various mechanisms that induce immune tolerance, angiogenesis, and increased dissemination of tumor cells. Yet monocytes can also give rise to antitumor effectors and activate antigen-presenting cells. This yin-yang activity relies on the plasticity of monocytes in response to environmental stimuli. In this review, we summarize current knowledge of the ontogeny, heterogeneity, and functions of monocytes and monocyte-derived cells in cancer, pinpointing the main pathways that are important for modeling the immunosuppressive tumor microenvironment.

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