Antibody mediated therapy targeting CD47 inhibits tumor progression of hepatocellular carcinoma

Xiao, Zhenyu; Chung, Haniee; Banan, Babak; Manning, Pamela T.; Ott, Katherine; Lin, Shin Ping; Capoccia, Benjamin J.; Subramanian, Vijay; Hiebsch, Ronald R.; Upadhya, Gundumi A.; Mohanakumar, Thalachallour; Frazier, William A.; Lin, Yiing; Chapman, William C.

doi:10.1016/j.canlet.2015.02.036

Cited by 136 publications

(93 citation statements)

References 15 publications

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“…Currently employed antibody therapeutic methods function via inducing antibody-dependent cellular cytotoxicity (ADCC), breaking pivotal receptor-ligand interactions, or other unknown mechanisms [34]. As described in several reports, CD47-SIRPα interactions constituted the main barrier that restricted antibodymediated killing efficiency of tumor cells [35][36][37][38]. Based on the results, we observed that the interaction of CD47 with SIRPα could be interrupted, at least partly, by CD47siRNA and anti-SIRPα (Fig.…”

Section: Discussionmentioning

confidence: 60%

CD47 is a Potential Target for the Treatment of Laryngeal Squamous Cell Carcinoma

Yang

Gao

Zhang

et al. 2016

Cell Physiol Biochem

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Background/Aims: This study aims to investigate the effect of CD47 on the development of laryngeal squamous cell carcinoma (LSCC) and the therapeutic potential of monoclonal antibody against CD47 and its ligand SIRPα in the treatment of LSCC. Methods: We firstly detected the expressions of CD47 mRNA and protein in LSCC and para-carcinoma tissues, introduced the most efficient CD47siRNA sequence into LSCC cells by lentiviral transfection and employed three monoclonal antibodies to evaluate their anti-LSCC effects in vitro and in vivo. Results: We observed that the mRNA and protein expressions of CD47 in LSCC tissue had significant increase in LSCC tissues compared with those in para-carcinoma tissue (p < 0.05). After the treatments of three monoclonal antibodies, i.e. anti-SIRPα, anti-CD47 BRIC126, anti-CD47 B6H12.2, in rats transfected with Hep-2 cell, it has been showed that the mRNA and protein expressions of CD47 in LSCC tissue decreased, macrophage efficiency was promoted when anti-SIRPα and/or CD47siRNA were used, the amounts, viabilities and expressions of CD47 protein of tumor cell were significantly inhibited. Additionally, combined use of CD47siRNA and anti-SIRPα seemed more efficient than solo use of CD47siRNA/anti-SIRPα. Conclusion: The results suggested a critical role of CD47 in LSCC development and the promising treatment of antiCD47/SIRPα and/or CD47siRNA in LSCC.

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Section: Discussionmentioning

confidence: 60%

CD47 is a Potential Target for the Treatment of Laryngeal Squamous Cell Carcinoma

Yang

Gao

Zhang

et al. 2016

Cell Physiol Biochem

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“…Macrophages can also recognize and phagocytose tumors cells upon down-regulation of CD47, a so-called “don’t eat me”-signal, on the tumor cell surface. However, many tumors up-regulate CD47 as an immune escape mechanism, including HCC (Xiao, et al, 2015). Accordingly, a study found that antibody-mediated blockade of CD47 enhances macrophage killing of HCC tumor cells.…”

Section: Cells Of the Hepatic Tumor Environment And Their Regulatimentioning

confidence: 99%

Tumor regulation of the tissue environment in the liver

Eggert

Greten

2017

Pharmacology & Therapeutics

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The tumor microenvironment (TME) in the liver plays an important role in primary and metastatic liver tumor formation and tumor growth promotion. Cellular and non-cellular components of the TME significantly influence tumor development, growth, metastatic spread, anti-tumor immunity and response to tumor therapy. The cellular components of the TME in the liver not only consist of infiltrating immune cells, but also of liver-resident cells such as liver sinusoidal endothelial cells (LSEC) and hepatic stellate cells (HSC), which promote tumor growth by negatively regulating tumor-associated immune responses. In this review, we characterize cells of the TME with pro- and anti-tumor function in primary and metastatic liver tumors. Furthermore, we summarize mechanisms that permit growth of hepatic tumors despite the occurrence of spontaneous anti-tumor immune responses and how novel therapeutic approaches targeting the TME could unleash tumor-specific immune responses to improve survival of liver cancer patients.

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“…In various xenograft tumor models using NOD-scid-IL2Rgamma null (NSG) mice, use of human CD47-blocking monoclonal antibodies has demonstrated superb efficacy against human acute lymphocytic leukemia, acute myeloid leukemia, leiomyosarcoma, and solid tumors [18, 20, 27, 28, 30, 31]. Most work initially concluded that the therapeutic effects of anti-human CD47 were dependent on the direct killing of the tumor by phagocytes.…”

Section: Introductionmentioning

confidence: 99%

Is CD47 an innate immune checkpoint for tumor evasion?

et al. 2017

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Cluster of differentiation 47 (CD47) (also known as integrin-associated protein) is a ubiquitously expressed glycoprotein of the immunoglobulin superfamily that plays a critical role in self-recognition. Various solid and hematologic cancers exploit CD47 expression in order to evade immunological eradication, and its overexpression is clinically correlated with poor prognoses. One essential mechanism behind CD47-mediated immune evasion is that it can interact with signal regulatory protein-alpha (SIRPα) expressed on myeloid cells, causing phosphorylation of the SIRPα cytoplasmic immunoreceptor tyrosine-based inhibition motifs and recruitment of Src homology 2 domain-containing tyrosine phosphatases to ultimately result in delivering an anti-phagocytic—“don’t eat me”—signal. Given its essential role as a negative checkpoint for innate immunity and subsequent adaptive immunity, CD47-SIRPα axis has been explored as a new target for cancer immunotherapy and its disruption has demonstrated great therapeutic promise. Indeed, CD47 blocking antibodies have been found to decrease primary tumor size and/or metastasis in various pre-clinical models. In this review, we highlight the various functions of CD47, discuss anti-tumor responses generated by both the innate and adaptive immune systems as a consequence of administering anti-CD47 blocking antibody, and finally elaborate on the clinical potential of CD47 blockade. We argue that CD47 is a checkpoint molecule for both innate and adaptive immunity for tumor evasion and is thus a promising target for cancer immunotherapy.

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Antibody mediated therapy targeting CD47 inhibits tumor progression of hepatocellular carcinoma

Cited by 136 publications

References 15 publications

CD47 is a Potential Target for the Treatment of Laryngeal Squamous Cell Carcinoma

CD47 is a Potential Target for the Treatment of Laryngeal Squamous Cell Carcinoma

Tumor regulation of the tissue environment in the liver

Is CD47 an innate immune checkpoint for tumor evasion?

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