Dominant B cell epitope from NY‐ESO‐1 recognized by sera from a wide spectrum of cancer patients: Implications as a potential biomarker

Abstract

Monitoring the spontaneous antibody (Ab) response against a panel of relevant tumor-associated antigens (TAA) in cancer patients may provide useful information regarding the clinical status of cancer. However, current Ab detection approaches require the purification of recombinant proteins, which is often difficult to achieve. In order to bypass the purification of recombinant proteins, we identified a dominant B-cell epitope from a shared tumor antigen NY-ESO- In the last 10 years, molecular identification of TAA has clearly demonstrated that the human immune system can react with endogenously arising cancer cells. 1 . Both the cellular and humoral arms of the human immune system recognize autologous TAA derived from cancer cells. 2,3 Of particular interest to the serological analysis of human cancers is the identification of TAA recognized by antibodies (Ab) present in the sera of cancer patients. 4 SEREX, or the serological analysis of recombinant cDNA expression libraries of human cancers, has been the primary approach to identify TAA based on their recognition by Ab. Up to now, there are at least 1,800 TAA identified based on recognition by Ab present in patients' sera. 5 . These TAA include targets from many cancer types, such as melanoma, renal cancer, Hodgkin's disease, esophageal cancer, lung cancer, colon cancer, gastric cancer, breast cancer, prostate cancer and so on. 3 The discovery of these TAA provides molecular details of the humoral immune response to autologous tumors. More importantly, the discovery of these molecules awakens the old hope of finding serological markers for cancer detection, diagnosis and prognosis. However, most of the SEREX-defined antigens do not or only react with few allogeneic sera. To investigate Ab responses against a large panel of TAA that covers a wide spectrum of patients with a particular cancer requires the purification of individual TAA protein, which is expensive and difficult to achieve. To circumvent the requirement of purifying individual protein, we propose identifying dominant B-cell epitopes from TAA for detection of Ab against TAA. We choose NY-ESO-1 as a prototype for identifying B-cell epitopes for the following reasons: 1) NY-ESO-1 is a cancer/testis antigen, which is expressed in a number of human cancers including those of the esophageal, 6 prostate, head and neck, lung, ovarian, breast, neuroblastoma, 7 gastric, as well as melanoma, hepatocellular carcinoma (HCC), T cell lymphoma and sarcoma. 8 Approximately 20 -30% of the above-mentioned cancers express the protein, and moreover, nearly 40 -50% of the patients with NY-ESO-1 expressing tumors develop antibodies against the protein. 9 2) Ab titers against NY-ESO-1 are driven by antigen expression of the endogenously arising tumor, and several studies have suggested that Ab titers against NY-ESO-1 correlated with advanced stages of the antigen-positive tumor in melanoma, transitional cell carcinoma and prostate cancer. 10 -12 3) Owing to its high immunogenicity and broad expression in a variety of ca...

B‐cell epitopes from the cancer testis antigen NY‐ESO‐1

“…We also analyzed the epitope specificity of anti-NY-ESO-1 antibodies in 12 sera from cancer patients (12 melanoma, 1 non small cell lung cancer, 1 breast cancer) using recombinant protein fragments of NY- and matrix-bound synthesized decamer peptides with 5 amino acid overlaps between every 2 consecutive decamer peptides covering the entire NY-ESO-1 molecule. Our results confirm the finding that most sera react with the epitope described by Zeng et al 1 However, our scanning of the entire NY-ESO-1 molecule irrespective of predicted hydrophilicity, surface accessibility and buried residues revealed that there is a second epitope against which IgG antibodies in 7 of the 12 anti-NY-ESO-1 antibodypositive sera were shown to react. This epitope is located between amino acids 96 and 125, with a core region to be assigned to p106-115 (Fig.…”

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Dear Sir,We read with great interest the article by Zeng et al 1 Basing their study on predictions of hydrophilicity, surface accessibility and buried residues, they restricted their search for NY-ESO-1 B-cell epitopes to the first N-terminal 74 amino acids and identified a dominant B-cell epitope that resides in the first 40 amino acids of the NY-ESO-1 molecule, with amino acids 11-30 representing the core of this B-cell epitope. We also analyzed the epitope specificity of anti-NY-ESO-1 antibodies in 12 sera from cancer patients (12 melanoma, 1 non small cell lung cancer, 1 breast cancer) using recombinant protein fragments of NY- and matrix-bound synthesized decamer peptides with 5 amino acid overlaps between every 2 consecutive decamer peptides covering the entire NY-ESO-1 molecule.

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Immunoproteomics: From biomarker discovery to diagnostic applications

“…While many studies show promising results, other studies illustrate significant limitations to the use of tumour antigens for cancer detection. For example, Zeng et al [78], showed that antibodies against a synthetic epitope of NY-ESO-1 occurred only in 5-10% of the serum samples from patients with different types of cancer. This implicates that in order to exploit antibody responses against tumour antigens for the detection of cancer, a large panel of tumour antigens or epitopes is required to cover a broad range of patients with a particular type of cancer.…”

Secretion and Immunogenicity of the Meningioma-Associated Antigen TXNDC16

“…Therefore, it is necessary to investigate potential immunogenic epitopes for tumor diagnosis, as demonstrated for cancer/testis Ag NY-ESO-1. Zeng et al (52) identified a 40-aa protein fragment of NY-ESO-1 recognized by autoantibodies in a wide range of patients' sera suffering from different tumor entities. In this study, we determined one TXNDC16 epitope exclusively recognized by autoantibodies in one-third of all tested meningioma sera and one epitope recognized in approximately one-fifth of meningioma sera but also in one control serum.…”