Immunotherapeutic Blockade of CD47 Inhibitory Signaling Enhances Innate and Adaptive Immune Responses to Viral Infection

Cham, Lamin B.; Dulgeroff, Laughing Bear Torrez; Tal, Michal Caspi; Adomati, Tom; Li, Fanghui; Bhat, Hilal; Huang, Anfei; Lang, Philipp A.; Moreno, Mary E.; Rivera, José; Galkina, Sofiya A.; Kosikova, Galina; Stoddart, Cheryl A.; McCune, Joseph M.; Myers, Lara; Lang, Karl S.; Hasenkrug, Kim J.

doi:10.1016/j.celrep.2020.03.058

Cited by 40 publications

(57 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, Tal et al and Cham et al reveals from their different modes of infections an upregulation of CD47 during in LCMV, Friend virus, VSV, HCV, HIV, La Crosse virus, SARS-CoV2, mycobacterium tuberculosis and other infections [ 12 ]. Unlike cancers, CD47 upregulation during infection stems from cytosolic or endosomal stimulation of pattern recognition receptors.…”

Section: Cd47 Expression and Infectionmentioning

confidence: 99%

“…CD47 is therefore important to balance the proinflammatory and anti-inflammatory signals. Indeed, we show that the virus infected cells induce increased CD47 level [ 12 ]. However, whether virus and other infectious agents can directly induce the infected cell to increase its CD47 expression to evade immune surveillance remains to be understood.…”

Section: Cd47 Expression and Infectionmentioning

confidence: 99%

“…In pathologic conditions, varieties of cancer cells are known to induce increased CD47 surface expression as a mechanism to evade macrophage mediated phagocytosis [ 9 , 10 , 11 ]. In addition to cancer, all immune cells upregulate CD47 upon pathogen invasion [ 12 ]. Typically, poxvirus has been shown to encode expression of CD47-like protein and this strongly inhibits the activation of macrophages and T cells.…”

Section: Introductionmentioning

confidence: 99%

“…The two most known interactions of CD47 is with signal regulatory protein alpha (SIRPa) and thrombospodin-1 (TSP-1). SIRPa is widely expressed on macrophages and dendritic cells while thrombonspondin-1 is a secreted matricellular glycoprotein [ 12 ]. The CD47-SIRPa interaction induces an antiphagocytic signal in macrophages and dendritic cells.…”

Section: Introductionmentioning

confidence: 99%

“…The CD47-SIRPa interaction induces an antiphagocytic signal in macrophages and dendritic cells. This interaction leads to the recruitment and activation of Src homology phosphate (SHP-1 and SHP-2) thereby inhibiting the myosin-IIA and this results in prevention of phagocytosis [ 12 , 15 ]. The mechanism of CD47-mediated suppression on innate immune cells is via the recruitment and activation of Src homology two domain-containing phosphatases, SHP-1 and SHP-2.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

CD47 as a Potential Target to Therapy for Infectious Diseases

Cham

Adomati

et al. 2020

Antibodies

Self Cite

View full text Add to dashboard Cite

The integrin associated protein (CD47) is a widely and moderately expressed glycoprotein in all healthy cells. Cancer cells are known to induce increased CD47 expression. Similar to cancer cells, all immune cells can upregulate their CD47 surface expression during infection. The CD47-SIRPa interaction induces an inhibitory effect on macrophages and dendritic cells (dendritic cells) while CD47-thrombospondin-signaling inhibits T cells. Therefore, the disruption of the CD47 interaction can mediate several biologic functions. Upon the blockade and knockout of CD47 reveals an immunosuppressive effect of CD47 during LCMV, influenza virus, HIV-1, mycobacterium tuberculosis, plasmodium and other bacterial pneumonia infections. In our recent study we shows that the blockade of CD47 using the anti-CD47 antibody increases the activation and effector function of macrophages, dendritic cells and T cells during viral infection. By enhancing both innate and adaptive immunity, CD47 blocking antibody promotes antiviral effect. Due to its broad mode of action, the immune-stimulatory effect derived from this antibody could be applicable in nonresolving and (re)emerging infections. The anti-CD47 antibody is currently under clinical trial for the treatment of cancer and could also have amenable therapeutic potential against infectious diseases. This review highlights the immunotherapeutic targeted role of CD47 in the infectious disease realm.

show abstract

Section: Cd47 Expression and Infectionmentioning

confidence: 99%

Section: Cd47 Expression and Infectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

CD47 as a Potential Target to Therapy for Infectious Diseases

Cham

Adomati

et al. 2020

Antibodies

Self Cite

View full text Add to dashboard Cite

show abstract

Bioconjugated Antibody‐Trojan Immune Converter Enhance Cancer Immunotherapy with Minimized Toxicity by Programmed Two‐Step Immunomodulation of Myeloid Cells

Park,

Jin,

Kim

et al. 2024

Adv Healthcare Materials

View full text Add to dashboard Cite

Current immune checkpoint blockade therapy (ICBT) predominantly targets T cells to harness the antitumor effects of adaptive immune system. However, the effectiveness of ICBT is reduced by immunosuppressive innate myeloid cells in tumor microenvironments (TMEs). Toll‐like receptor 7/8 agonists (TLR7/8a) are often used to address this problem because they can reprogram myeloid‐derived suppressor cells (MDSCs) and tumor‐associated M2 macrophages, and boost dendritic cell (DC)‐based T‐cell generation; however, the systemic toxicity of TLR7/8a limits its clinical translation. Here, to address this limitation and utilize the effectiveness of TLR7/8a, we suggested a programmed two‐step activation strategy via Antibody‐Trojan Immune Converter Conjugates (ATICC) that specifically targeted myeloid cells by anti‐SIRPα followed by reactivation of transiently inactivated Trojan TLR7/8a after antibody‐mediated endocytosis. The ATICC blocked the CD47‐SIRPα (“don't eat me” signal), enhanced phagocytosis, reprogrammed M2 macrophages and MDSCs, and increased cross‐presentation by DCs, resulting in antigen‐specific CD8+ T‐cell generation in tumor‐draining lymph nodes and TME while minimizing systemic toxicity. The local or systemic administration of ATICC improved ICBT responsiveness through reprogramming of the immunosuppressive TME, increased infiltration of antigen‐specific CD8+ T cells, and antibody‐dependent cellular phagocytosis. Our results highlighted the programmed and targeted immunomodulation via ATICC could enhance cancer immunotherapy with minimized systemic toxicities.This article is protected by copyright. All rights reserved

show abstract

Exosomes: Promising nanocarrier for cancer therapy

Zhao

Tao

et al. 2021

Nano Select

View full text Add to dashboard Cite

Cancer has intensively threatened the health and life of human beings across the world. Drug delivery systems (DDSs) can protect the packaged cargoes from degradation; effectively delivery cargoes to specific tissues. Most DDSs are based on functional nanomaterials. As natural nanomaterials, exosomes are secreting by mammalian cells through the multivesicle bodies route. Usually, exosomes possess uniform size ranging from 50 to 150 nm, their membrane surface has many functional proteins and cavity contains RNA, DNA similar to maternal cells. Owing to the high biocompatibility, excellent penetration capability as well as ease to be engineered, exosomes have shown outstanding potentials in delivering therapeutic molecules for cancer diagnosis and treatment. This review summarizes the unique characteristics which makes exosomes promising nanocarrier for cancer treatment. The future developments of exosomes based biomedical applications towards cancer are also outlined. We expect the review will help readers understand the potential value of exosomes based nanocarrier, and also try to elaborate their promising applications.

show abstract

Immunotherapeutic Blockade of CD47 Inhibitory Signaling Enhances Innate and Adaptive Immune Responses to Viral Infection

Cited by 40 publications

References 48 publications

CD47 as a Potential Target to Therapy for Infectious Diseases

CD47 as a Potential Target to Therapy for Infectious Diseases

Bioconjugated Antibody‐Trojan Immune Converter Enhance Cancer Immunotherapy with Minimized Toxicity by Programmed Two‐Step Immunomodulation of Myeloid Cells

Exosomes: Promising nanocarrier for cancer therapy

Contact Info

Product

Resources

About