Effect of CD47 Blockade on Vascular Inflammation

Jarr, Kai-Uwe; Nakamoto, Ryusuke; Doan, Brandon H.; Kojima, Yoshiyuki; Weissman, Irving L.; Advani, Ranjana H.; Iagaru, Andrei; Leeper, Nicholas J.

doi:10.1056/nejmc2029834

Cited by 54 publications

(40 citation statements)

References 5 publications

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“…Delineating the exact mechanism of action of the target molecules would be very helpful in overcoming the side effects or applying the appropriate treatment according to the situation and environment of each patient. In addition to the antibodies mentioned in the text, development and clinical trials of antibodies that inhibit a variety of molecules continue, such as ANGPTL family, CD47, CD31 [ 138 , 139 , 140 , 141 ]. Through these efforts, more targets will be found in the future, and mediators such as specific antibodies will be developed and eventually lead to the conquering of many diseases.…”

Section: Discussionmentioning

confidence: 99%

Antibody-Based Therapeutics for Atherosclerosis and Cardiovascular Diseases

Lee

2021

IJMS

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Cardiovascular disease is the leading cause of death worldwide, and its prevalence is increasing due to the aging of societies. Atherosclerosis, a type of chronic inflammatory disease that occurs in arteries, is considered to be the main cause of cardiovascular diseases such as ischemic heart disease or stroke. In addition, the inflammatory response caused by atherosclerosis confers a significant effect on chronic inflammatory diseases such as psoriasis and rheumatic arthritis. Here, we review the mechanism of action of the main causes of atherosclerosis such as plasma LDL level and inflammation; furthermore, we review the recent findings on the preclinical and clinical effects of antibodies that reduce the LDL level and those that neutralize the cytokines involved in inflammation. The apolipoprotein B autoantibody and anti-PCSK9 antibody reduced the level of LDL and plaques in animal studies, but failed to significantly reduce carotid inflammation plaques in clinical trials. The monoclonal antibodies against PCSK9 (alirocumab, evolocumab), which are used as a treatment for hyperlipidemia, lowered cholesterol levels and the incidence of cardiovascular diseases. Antibodies that neutralize inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-17, and IL-12/23) have shown promising but contradictory results and thus warrant further research.

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Section: Discussionmentioning

confidence: 99%

Antibody-Based Therapeutics for Atherosclerosis and Cardiovascular Diseases

Lee

2021

IJMS

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“…CD47 protects healthy cells from the immune system by binding to the n terminal of the immune cell signal-regulating protein a (SIRPa), signaling "don't eat me" and inhibiting the phagocytosis of macrophages. In the meantime, CD47, as a "don't eat me" signal, protects tumor cells from phagocytosis by macrophages, which has become a new mechanism of tumor development and development, and has also explored a new effective way for tumor immunotherapy (61,62). CD47 antibodies target a variety of indications, including hematological malignancies such as non-Hodgkin Lymphoma and acute myeloid leukemia (AML), as well as solid tumors such as colorectal cancer, ovarian, and bladder cancers (63).…”

Section: Cd47mentioning

confidence: 99%

The Mechanism of Stimulating and Mobilizing the Immune System Enhancing the Anti-Tumor Immunity

Zhu

2021

Front. Immunol.

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Cancer immunotherapy is a kind of therapy that can control and eliminate tumors by restarting and maintaining the tumor-immune cycle and restoring the body’s normal anti-tumor immune response. Although immunotherapy has great potential, it is currently only applicable to patients with certain types of tumors, such as melanoma, lung cancer, and cancer with high mutation load and microsatellite instability, and even in these types of tumors, immunotherapy is not effective for all patients. In order to enhance the effectiveness of tumor immunotherapy, this article reviews the research progress of tumor microenvironment immunotherapy, and studies the mechanism of stimulating and mobilizing immune system to enhance anti-tumor immunity. In this review, we focused on immunotherapy against tumor microenvironment (TME) and discussed the important research progress. TME is the environment for the survival and development of tumor cells, which is composed of cell components and non-cell components; immunotherapy for TME by stimulating or mobilizing the immune system of the body, enhancing the anti-tumor immunity. The checkpoint inhibitors can effectively block the inhibitory immunoregulation, indirectly strengthen the anti-tumor immune response and improve the effect of immunotherapy. We also found the checkpoint inhibitors have brought great changes to the treatment model of advanced tumors, but the clinical treatment results show great individual differences. Based on the close attention to the future development trend of immunotherapy, this study summarized the latest progress of immunotherapy and pointed out a new direction. To study the mechanism of stimulating and mobilizing the immune system to enhance anti-tumor immunity can provide new opportunities for cancer treatment, expand the clinical application scope and effective population of cancer immunotherapy, and improve the survival rate of cancer patients.

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“…Efferocytosis (the removal of inflamed and dying cells by phagocytosis) is recognized as a hallmark of atherosclerosis and is caused in part by the pathologic upregulation of the antiphagocytic signal molecule CD47 [69,74,75]. In preclinical studies, CD47 downregulation therapy was shown to reduce atherosclerotic burden and plaque rupture [74], and the humanized anti-CD47 antibody magrolimab might reduce vascular inflammation, as quantified by 18F-FDG uptake in the carotid arteries [75,76]. Some drugs, such as HMG-CoA reductase inhibitors (statins), reduced the risk of adverse cardiovascular effects by counteracting detrimental epigenetic modifications that might have occurred in monocytederived macrophages [77].…”

Section: Mending Detrimental Epigenetic Changesmentioning

confidence: 99%

Epigenetics and Medicine

Cocco¹,

Amiet²

2021

obm genet

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“Epigenetics is the study of how your behaviors and environment can cause changes that affect the way your genes work. Unlike genetic changes, epigenetic changes are reversible and do not change your DNA sequence, but they can change how your body reads a DNA sequence” (https://www.cdc.gov/genomics/disease/epigenetics.htm). Epigenetic interactions, along with the genetic expression in innate cells, change the structure and function of chromatin, and thus, turn the genes on and off. Epigenetic changes influence disease load and resistance and play an important role in health maintenance and almost all medical disorders, and differs significantly with sex and ethnicity. Epigenetic changes may have either positive or detrimental effects on the immune system. They are long-lasting, increase a host’s susceptibility to infections and medical pathologies, and affect the efficacy of vaccines. Recent studies have indicated that detrimental epigenetic changes can be mended. Safe and effective mechanisms to reverse detrimental epigenetic scars will have broad medical implications, decrease mortality after infections, and protect the elderly against infections, autoimmune diseases, and cancer. These therapies might be useful for the successful application of vaccines in countries where HIV, parasite infestation, malaria, and other chronic diseases are endemic, and also for a better effect of vaccines in geriatric patients.

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Effect of CD47 Blockade on Vascular Inflammation

Cited by 54 publications

References 5 publications

Antibody-Based Therapeutics for Atherosclerosis and Cardiovascular Diseases

Antibody-Based Therapeutics for Atherosclerosis and Cardiovascular Diseases

The Mechanism of Stimulating and Mobilizing the Immune System Enhancing the Anti-Tumor Immunity

Epigenetics and Medicine

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