Fine-mapping naturally occurring NY-ESO-1 antibody epitopes in melanoma patients’ sera using short overlapping peptides and full-length recombinant protein

Komatsu, Nobukazu; Jackson, Heather; Chan, Kok Fei; Oveissi, Sara; Cebon, Jonathan; Itoh, Kyogo; Chen, Weisan

doi:10.1016/j.molimm.2013.01.014

Cited by 9 publications

(11 citation statements)

References 24 publications

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“…However, the ratio of NY‐ESO‐1 to CTAG2 autoantibody titres was found to vary considerably across individual patients, suggesting that different patients raised autoantibodies to different epitopes along the length of the NY‐ESO‐1 protein (Fig. ), in agreement with previous observations …”

Section: Resultssupporting

confidence: 92%

Development of a novel, quantitative protein microarray platform for the multiplexed serological analysis of autoantibodies to cancer-testis antigens

et al. 2014

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The cancer-testis antigens are a group of unrelated proteins aberrantly expressed in various cancers in adult somatic tissues. This aberrant expression can trigger spontaneous immune responses, a phenomenon exploited for the development of disease markers and therapeutic vaccines. However, expression levels often vary amongst patients presenting the same cancer type, and these antigens are therefore unlikely to be individually viable as diagnostic or prognostic markers. Nevertheless, patterns of antigen expression may provide correlates of specific cancer types and disease progression. Herein, we describe the development of a novel, readily customizable cancer-testis antigen microarray platform together with robust bioinformatics tools, with which to quantify anti-cancer testis antigen autoantibody profiles in patient sera. By exploiting the high affinity between autoantibodies and tumor antigens, we achieved linearity of response and an autoantibody quantitation limit in the pg/mL range-equating to a million-fold serum dilution. By using oriented attachment of folded, recombinant antigens and a polyethylene glycol microarray surface coating, we attained minimal non-specific antibody binding. Unlike other proteomics methods, which typically use lower affinity interactions between monoclonal antibodies and tumor antigens for detection, the high sensitivity and specificity realized using our autoantibody-based approach may facilitate the development of better cancer biomarkers, as well as potentially enabling pre-symptomatic diagnosis. We illustrated the usage of our platform by monitoring the response of a melanoma patient cohort to an experimental therapeutic NY-ESO-1-based cancer vaccine; inter alia, we found evidence of determinant spreading in individual patients, as well as differential CT antigen expression and epitope usage.

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Section: Resultssupporting

confidence: 92%

Development of a novel, quantitative protein microarray platform for the multiplexed serological analysis of autoantibodies to cancer-testis antigens

et al. 2014

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“…However, these methods are time consuming, expensive for fine epitope mapping, and cannot identify immunodominant epitopes in the SEB antigen. Therefore, overlapping peptides, in combination with computational methods that are low cost and highly efficient, were rationally employed to identify linear B cell epitopes [34].…”

Section: Discussionmentioning

confidence: 99%

Fine-Mapping of Immunodominant Linear B-Cell Epitopes of the Staphylococcus Aureus SEB Antigen Using Short Overlapping Peptides

Zhao

Sun

et al. 2014

PLoS ONE

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Staphylococcal enterotoxin B (SEB) is one of the most potent Staphylococcus aureus exotoxins (SEs). Due to its conserved sequence and stable structure, SEB might be a good candidate antigen for MRSA vaccines. Although cellular immune responses to SEB are well-characterized, much less is known regarding SEB-specific humoral immune responses, particularly regarding detailed epitope mapping. In this study, we utilized a recombinant nontoxic mutant of SEB (rSEB) and an AlPO4 adjuvant to immunize BALB/c mice and confirmed that rSEB can induce a high antibody level and effective immune protection against MRSA infection. Next, the antisera of immunized mice were collected, and linear B cell epitopes within SEB were finely mapped using a series of overlapping synthetic peptides. Three immunodominant B cell epitopes of SEB were screened by ELISA, including a novel epitope, SEB205-222, and two known epitopes, SEB97–114 and SEB247-261. Using truncated peptides, an ELISA was performed with peptide-KLH antisera, and the core sequence of the three immunodominant B cell epitopes were verified as SEB97-112, SEB207-222, and SEB247-257. In vitro, all of the immunodominant epitope-specific antisera (anti-SEB97-112, anti-SEB207-222 and anti-SEB247-257) were observed to inhibit SEB-induced T cell mitogenesis and cytokine production from splenic lymphocytes of BALB/c mice. The homology analysis indicated that SEB97–112 and SEB207-222 were well-conserved among different Staphylococcus aureus strains. The 3D crystal structure of SEB indicated that SEB97–112 was in the loop region inside SEB, whereas SEB207-222 and SEB247-257 were in the β-slice region outside SEB. In summary, the fine-mapping of linear B-cell epitopes of the SEB antigen in this study will be useful to understand anti-SEB immunity against MRSA infection further and will be helpful to optimize MRSA vaccine designs that are based on the SEB antigen.

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“…Spontaneous autoantibodies are present in patients with a variety of malignancies (5); however, whether such Abs support or inhibit immune-mediated tumor control is debated (6–8) Spontaneous Ab to the cancer testis antigen NY-ESO-1 (9) has been detected in about 50% of patients with NY-ESO-1-expressing melanomas while undetectable in patients with NY-ESO-1 negative tumors and in healthy adults (10) and have been associated with tumor progression (11). Several studies have reported clinical benefits in patients with an integrated humoral (Ab) and cellular response to cancer vaccines or to CTLA4 blockade (12–14), whereas others have not identified clinical impact of Abs induced by cancer vaccines (15, 16).…”

Section: Introductionmentioning

confidence: 99%

Vaccination with Melanoma Helper Peptides Induces Antibody Responses Associated with Improved Overall Survival

Reed¹,

Cresce²,

Mauldin³

et al. 2015

Clin Cancer Res

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Purpose A melanoma vaccine incorporating six peptides designed to induce helper T cell responses to melanoma antigens has induced Th1-dominant CD4+ T cell responses in most patients, and induced durable clinical responses or stable disease in 24% of evaluable patients. The present study tested whether this vaccine also induced antibody (Ab) responses to each peptide, and whether Ab responses were associated with T cell responses and with clinical outcome. Patients and Methods Serum samples were studied from 35 patients with stage III–IV melanomas vaccinated with 6 melanoma helper peptides (6MHP). IgG Ab responses were measured by ELISA. Associations with immune response and overall survival were assessed by log-rank test and Chi square analysis of Kaplan-Meier data. Results Ab responses to 6MHP were detected by week 7 in 77% of patients, and increased to peak 6 weeks after the last vaccine and persisted to 6 months. Ab responses were induced most frequently to longer peptides. Of those with T cell responses, 82% had early Ab responses. Survival was improved for patients with early Ab response (p = 0.0011) or with early T cell response (p < 0.006), and was best for those with both Ab and T cell responses (p = 0.0002). Conclusion Vaccination with helper peptides induced both Ab responses and T cell responses, associated with favorable clinical outcome. Such immune responses may predict favorable clinical outcome to guide combination immunotherapy. Further studies are warranted to understand mechanisms of interaction of these Abs, T cell responses, and tumor control.

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Fine-mapping naturally occurring NY-ESO-1 antibody epitopes in melanoma patients’ sera using short overlapping peptides and full-length recombinant protein

Cited by 9 publications

References 24 publications

Development of a novel, quantitative protein microarray platform for the multiplexed serological analysis of autoantibodies to cancer-testis antigens

Development of a novel, quantitative protein microarray platform for the multiplexed serological analysis of autoantibodies to cancer-testis antigens

Fine-Mapping of Immunodominant Linear B-Cell Epitopes of the Staphylococcus Aureus SEB Antigen Using Short Overlapping Peptides

Vaccination with Melanoma Helper Peptides Induces Antibody Responses Associated with Improved Overall Survival

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