Identification of the epitope of 10-7G glycan antibody to recognize cancer-associated haptoglobin

Morishita, Koichi; Maki, Yuta; Takamatsu, Shinji; Ito, Nami; Koda, Sayaka; Motooka, Kei; Kamada, Y.; Kajihara, Yasuhiro; Miyoshi, Eiji

doi:10.1016/j.ab.2020.113588

Cited by 7 publications

(6 citation statements)

References 21 publications

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“…Гликозилирование -одна из распространённых и важных ПТМ, создающих многочисленные белковые варианты за счёт олигосахаридной гетерогенности, которая влияет на физические (растворимость, стабильность), структурные (фолдинг) и функциональные свойства белков [32,86] [113]. Также был показан значительно повышенный уровень фукозилированного Hp (F-Hp) в сыворотке пациентов с раком поджелудочной железы и даже получены моноклональные антитела, высокоспецифичные к форме F-Hp, присутствующей у пациента [114,115].…”

Section: гаптоглобин и его протеоформы как потенциальные биомаркеры заболеванийunclassified

Haptoglobin as a biomarker

Naryzhny

Legina

2021

BIOMED KHIM

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Haptoglobin (Hp) is a blood plasma glycoprotein that binds free hemoglobin (Hb) and plays a critical role in tissue protection and the prevention of oxidative damage. In addition, it has a number of regulatory functions. Haptoglobin is an acute phase protein, its concentration in plasma changes in pathology, and the test for its concentration is part of normal clinical practice. Haptoglobin is a conservative protein synthesized mainly in the liver and lungs and is the subject of research as a potential biomarker of many diseases, including various forms of malignant neoplasms. Haptoglobin has several unique biophysical characteristics. Only in humans, the Hp gene is polymorphic, has three structural alleles that control the synthesis of three major phenotypes of Hp, homozygous Hp1-1 and Hp2-2, and heterozygous Hp2-1, determined by a combination of allelic variants that are inherited. Numerous studies indicate that the phenotype of haptoglobin can be used to judge the individual's predisposition to various diseases. In addition, Hp undergoes various post-translational modifications (PTMs). These are structural transformations (removal of the signal peptide, cutting of the Pre-Hp precursor molecule into two subunits, α and β, limited proteolysis of α-chains, formation of disulfide bonds, multimerization), as well as chemical modifications of α-chains and glycosylation of the β-chain. Glycosylation of the β-chain of haptoglobin at four Asn sites is the most important variable PTM that regulates the structure and function of the glycoprotein. The study of modified oligosaccharides of the Hp β-chain has become the main direction in the study of pathological processes, including malignant neoplasms. Many studies are focused on the identification of PTM and changes in the level of the α2-chain of this protein in pathology. These characteristics of Hp indicate the possibility of the existence of this protein as different proteoforms, probably with different functions. This review is devoted to the description of the structural and functional diversity of Hp and its potential use as a biomarker of various pathologies.

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Section: гаптоглобин и его протеоформы как потенциальные биомаркеры заболеванийunclassified

Haptoglobin as a biomarker

Naryzhny

Legina

2021

BIOMED KHIM

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“…We previously developed lectin Aleuria Aurantia Lectin (AAL) and 10-7G monoclonal antibodies that mainly recognise Fuc-mHp and Fuc-pHp, respectively (see Supplementary Fig. S1 online) 13 .…”

Section: Resultsmentioning

confidence: 99%

“…A total of 1 mL of plasma was used for ELISA. Aleuria Aurantia Lectin (AAL)-Hp, 10-7G, and total-Hp ELISA were performed using in-house pipelines described previously 12 , 13 .…”

Section: Methodsmentioning

confidence: 99%

“…In the present study, we evaluated serum Fuc-mature Hp (Fuc-mHp) and Fuc-pro Hp (Fuc-pHp) levels in patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab (anti-programmed death protein 1 [PD-1] antibody) using our developed antibodies 13 . Furthermore, we investigated whether Fuc-Hp levels can be a potential biomarker for predicting the clinical prognosis in mRCC patients with ICI treatment.…”

Section: Introductionmentioning

confidence: 99%

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Prognostic significance of serum fucosylated pro-haptoglobin in advanced renal cell carcinoma patients treated with immune checkpoint inhibitors

Kato,

Morishita,

Tomiyama

et al. 2023

Sci Rep

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With the widespread use of immune checkpoint inhibitors (ICIs), identifying predictive biomarkers is critical. Recently, serum fucosylated haptoglobin (Fuc-Hp) was thought to play an important role in tumour immunity in several types of cancer. Therefore, evaluating serum Fuc-Hp in the peripheral blood can potentially identify non-invasive predictive biomarkers for the clinical efficacy of ICIs. In this study, 31 patients with advanced renal cell carcinoma (RCC) treated with nivolumab were enrolled and defined as responders or non-responders according to RECIST criteria. Serum samples were collected before and 1 month after treatment initiation, and an ELISA assay was performed using Aleuria Aurantia Lectin (AAL) and 10-7G monoclonal antibodies that recognise Fuc-mature Hp (Fuc-mHp) and Fuc-pro Hp (Fuc-pHp), respectively. We first measured AAL-haptoglobin (Fuc-mHp) and total haptoglobin levels before nivolumab and found that neither value could predict the clinical response. Notably, serum 10-7G levels were significantly lower in the responder group (p = 0.035). We also confirmed the use of serum 10-7G levels for predicting progressive disease after nivolumab (area under the curve, 0.816). Accordingly, low 10-7G levels were significantly correlated with better progression-free survival (p = 0.041). In conclusion, serum Fuc-pHp analysis may identify patients with advanced RCC who benefit from ICIs.

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“…Aberrant glycoforms can reflect changes in Hp function in the skin and be used as a marker of the disease [ 113 ]. A significantly increased level of fucosylated Hp (F-Hp) in the serum of patients with pancreatic cancer was also shown, and even monoclonal antibodies highly specific to the form of F-Hp present in the patient were obtained [ 114 , 115 ].…”

Section: Haptoglobin and Its Proteoforms As Potential Biomarkers Of Diseasesmentioning

confidence: 99%

Haptoglobin as a Biomarker

Naryzny

Legina

2021

Biochem. Moscow Suppl. Ser. B

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— Haptoglobin (Hp) is a glycoprotein that binds free hemoglobin (Hb) in plasma and plays a critical role in tissue protection and prevention of oxidative damage. Besides, it has some regulatory functions. Haptoglobin is an acute-phase protein, its concentration in plasma changes in pathology, and the test for its concentration is part of normal clinical practice. Haptoglobin is a conservative protein synthesized mainly in the liver and lungs and is the subject of research as a potential biomarker of many diseases, including various forms of malignant neoplasms. Haptoglobin has several unique biophysical characteristics. The human Нр gene is polymorphic, has three structural alleles that control the synthesis of three major phenotypes of haptoglobin: homozygous Нр1-1 and Нр2-2, and heterozygous Нр2-1, determined by a combination of allelic variants that are inherited. Numerous studies indicate that the phenotype of haptoglobin can be used to judge the individual predisposition of a person to various diseases. In addition, Hp undergoes various post-translational modifications (PTMs). These are structural transformations (removal of the signal peptide, cutting off the Pre-Hp precursor molecule into two subunits, α and β, limited proteolysis of α-chains, formation of disulfide bonds, multimerization), as well as chemical modifications of α-chains and glycosylation of the β-chain. Glycosylation of the β-chain of haptoglobin at four Asn sites is the most important variable PTM that regulates the structure and function of the glycoprotein. The study of modified oligosaccharides of the β-chain of Hp has become the main direction in the study of pathological processes, including malignant neoplasms. These characteristics indicate the possibility of the existence of Hp in the form of a multitude of proteoforms, probably performing different functions. This review is devoted to the description of the structural and functional diversity and the potential use of Hp as a biomarker of various pathologies.

show abstract

Identification of the epitope of 10-7G glycan antibody to recognize cancer-associated haptoglobin

Cited by 7 publications

References 21 publications

Haptoglobin as a biomarker

Haptoglobin as a biomarker

Prognostic significance of serum fucosylated pro-haptoglobin in advanced renal cell carcinoma patients treated with immune checkpoint inhibitors

Haptoglobin as a Biomarker

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