Epitope Mapping of Monoclonal Antibodies to Keratin 19 Using Keratin Fragments, Synthetic Peptides and Phage Peptide Libraries

Böttger, Volker; Stasiak, Pauline C.; Harrison, Dolores L.; Mellerick, Dervla M.; Lane, E. Birgitte

doi:10.1111/j.1432-1033.1995.0475e.x

Cited by 10 publications

(3 citation statements)

References 35 publications

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“…Attempts to identify a linear peptide epitope via peptide ELISA have failed. Linear peptide libraries may fail to reveal antibody binding as the epitope can have a structure with a high conformational constraint, which cannot be adopted by short peptides [17]. On the other hand, binding on a Western blot does not exclude a conformational epitope, since renaturation of proteins occurs on the blot if immersed in PBS.…”

Section: Discussionmentioning

confidence: 99%

A Monoclonal Antibody to Lewis Y/Lewis b Revealing Mimicry of the Histone H1 to Carbohydrate Structures

et al. 2007

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Antibodies to either peptide or carbohydrate tumour antigens are established tools for diagnostics and therapy. We here describe an antibody (A70‐A/A9) recognizing a carbohydrate epitope common to the tumour‐associated Lewis Y and Lewis b antigens (Fucα1‐2Galβ1‐4/3[Fucα1‐3/4]GlcNAcβ‐). Its specificity was established without doubt with a panel of 86 synthetic mono‐ and oligosaccharidic structures. This antibody was found to cross‐react with the nuclear protein histone H1. Binding to H1 was specific, periodate‐insensitive (non‐carbohydrate) and saturable. Histone H1 was able to inhibit Lewis Y binding very effectively in a concentration‐dependent manner. We conclude that it represents an example of natural peptide mimicry of a carbohydrate epitope. It may explain the observed occurrence of ‘anti‐histone autoantibodies’ in cancer patients.

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Section: Discussionmentioning

confidence: 99%

A Monoclonal Antibody to Lewis Y/Lewis b Revealing Mimicry of the Histone H1 to Carbohydrate Structures

et al. 2007

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“…Serum concentrations of Cyfra 21.1 were measured using a specific immunoradiometric assay (IRMA, ELISA-CYFRA, Cisbio Bioassay, Codolet, France), in which Cyfra 21.1 molecules are sandwiched between the two mouse monoclonal antibodies KS 19.1 and BM 19.21 [ 17 , 18 ]. Excess unbound tracer was easily removed during the washing step, and the ELISA retained only the absorbed antibody/antigen/tracer antibody combination.…”

Section: Methodsmentioning

confidence: 99%

Serum CYFRA 21.1 Level Predicts Disease Course in Thyroid Cancer with Distant Metastasis

Jeong

Lee

Yoon

et al. 2021

Cancers

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Background: Serum Cyfra 21.1, the soluble fragment of CK19, has been used as a prognostic tumor marker in various cancers, indicating poor tumor differentiation and increased metastasis. Methods: We analyzed the serum Cyfra 21.1 level in 51 consecutive patients with thyroid cancer manifesting distant metastasis treated with prior total thyroidectomy. Serum Cyfra 21.1 levels of 26 thyroid cancer patients without metastasis and 50 healthy individuals were used for comparison. Results: Higher serum Cyfra 21.1 levels were detected in thyroid cancer patients with distant metastasis compared with healthy subjects and thyroid cancer patients without metastasis (p = 0.012). Serum Cyfra 21.1 levels were significantly increased in patients with positive BRAF V600E mutation (p = 0.019), undergoing Tyrosine Kinase Inhibitor (TKI) therapy (p = 0.008), with radioiodine-refractory status (p = 0.047), and in disease progression compared with those manifesting stable disease (p = 0.007). In progressive disease with undetectable or unmonitored thyroglobulin because of thyroglobulin antibody, serum Cyfra 21.1 was useful as a biomarker for follow-up of disease course. Conclusion: Serum Cyfra 21.1 in thyroid cancer patients might represent an alternative biomarker predicting tumor progression, especially in cases not associated with serum Tg levels.

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“…There are a large number of commercially available K19 antibodies that target various epitopes, of which RCK108 and BA17 are most commonly used. The epitope of the RCK108 antibody is closer to the N-terminus of K19, between amino acid residues 112 and 153, while the epitope of the BA17 antibody is in the C-terminal region of K19, between amino acid residues 360 and 395 [64]. The immunoreactivities of the 2 abovementioned antibodies are closely correlated; however, discordance in the staining proportion and intensity has been reported in breast cancer and pancreatic neuroendocrine tumors [65, 66].…”

Section: Evaluation Of K19 Expression In the Tissue And Serum Of Patimentioning

confidence: 99%

Clinico-Radio-Pathological and Molecular Features of Hepatocellular Carcinomas with Keratin 19 Expression

Rhee¹,

Kim²,

Park³

2020

Liver Cancer

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Hepatocellular carcinoma (HCC) is a heterogeneous neoplasm, both from the molecular and histomorphological aspects. One example of heterogeneity is the expression of keratin 19 (K19) in a subset (4–28%) of HCCs. The presence of K19 expression in HCCs has important clinical implications, as K19-positive HCCs have been associated with aggressive tumor biology and poor prognosis. Histomorphologically, K19-positive HCCs demonstrate a more infiltrative appearance, poor histological differentiation, more frequent vascular invasion, and more intratumoral fibrous stroma than K19-negative conventional HCCs. From the molecular aspect, K19-positive HCCs have been matched with various gene signatures that have been associated with stemness and poor prognosis, including the G1–3 groups, S2 class, cluster A, proliferation signature, and vascular invasion signature. K19-positive HCCs also show upregulated signatures related to transforming growth factor-β pathway and epithelial-to-mesenchymal transition. The main regulators of K19 expression include hepatocyte growth factor-MET paracrine signaling by cancer-associated fibroblast, epidermal growth factor-epidermal growth factor receptor signaling, laminin, and DNA methylation. Clinically, higher serum alpha-fetoprotein levels, frequent association with chronic hepatitis B, more invasive growth, and lymph node metastasis have been shown to be characteristics of K19-positive HCCs. Radiologic features including atypical enhancement patterns, absence of tumor capsules, and irregular tumor margins can be a clue for K19-positive HCCs. From a therapeutic standpoint, K19-positive HCCs have been associated with poor outcomes after curative resection or liver transplantation, and resistance to systemic chemotherapy and locoregional treatment, including transarterial chemoembolization and radiofrequency ablation. In this review, we summarize the currently available knowledge on the clinico-radio-pathological and molecular features of K19-expressing HCCs, including a detailed discussion on the regulation mechanism of these tumors.

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Epitope Mapping of Monoclonal Antibodies to Keratin 19 Using Keratin Fragments, Synthetic Peptides and Phage Peptide Libraries

Cited by 10 publications

References 35 publications

A Monoclonal Antibody to Lewis Y/Lewis b Revealing Mimicry of the Histone H1 to Carbohydrate Structures

A Monoclonal Antibody to Lewis Y/Lewis b Revealing Mimicry of the Histone H1 to Carbohydrate Structures

Serum CYFRA 21.1 Level Predicts Disease Course in Thyroid Cancer with Distant Metastasis

Clinico-Radio-Pathological and Molecular Features of Hepatocellular Carcinomas with Keratin 19 Expression

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