Identification of CD4+ T Cell Epitopes from NY-ESO-1 Presented by HLA-DR Molecules

Zeng, Gang; Touloukian, Christopher E.; Wang, Xiang; Restifo, Nicholas P.; Rosenberg, Steven A.; Wang, Rong Fu

doi:10.4049/jimmunol.165.2.1153

Cited by 128 publications

(88 citation statements)

References 41 publications

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“…Additionally, it may be possible to up-regulate NY-ESO-1 expression in cancer patients by treatment with drugs that induce DNA demethylation (38,39). Finally, we have identified MHC class II-restricted NY-ESO-1 TCR epitopes (22,40,41), and we are currently attempting to simultaneously engineer a population of T cells with both class Iand class II-restricted TCRs. …”

Section: Discussionmentioning

confidence: 99%

Primary Human Lymphocytes Transduced with NY-ESO-1 Antigen-Specific TCR Genes Recognize and Kill Diverse Human Tumor Cell Lines

Zhao

Zheng

Robbins

et al. 2005

The Journal of Immunology

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cDNAs encoding TCR α- and β-chains specific for HLA-A2-restricted cancer-testis Ag NY-ESO-1 were cloned using a 5′RACE method from RNA isolated from a CTL generated by in vitro stimulation of PBMC with modified NY-ESO-1-specific peptide (p157–165, 9V). Functionality of the cloned TCR was confirmed by RNA electroporation of primary PBL. cDNA for these α- and β-chains were used to construct a murine stem cell virus-based retroviral vector, and high titer packaging cell lines were generated. Gene transfer efficiency in primary T lymphocytes of up to 60% was obtained without selection using a method of precoating retroviral vectors onto culture plates. Both CD4+ and CD8+ T cells could be transduced at the same efficiency. High avidity Ag recognition was demonstrated by coculture of transduced lymphocytes with target cells pulsed with low levels of peptide (<20 pM). TCR-transduced CD4 T cells, when cocultured with NY-ESO-1 peptide pulsed T2 cells, could produce IFN-γ, GM-CSF, IL-4, and IL-10, suggesting CD8-independent, HLA-A2-restricted TCR activation. The transduced lymphocytes could efficiently recognize and kill HLA-A2- and NY-ESO-1-positive melanoma cell lines in a 4-h 51Cr release assay. Finally, transduced T cells could efficiently recognize NY-ESO-1-positive nonmelanoma tumor cell lines. These results strongly support the idea that redirection of normal T cell specificity by TCR gene transfer can have potential applications in tumor adoptive immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Primary Human Lymphocytes Transduced with NY-ESO-1 Antigen-Specific TCR Genes Recognize and Kill Diverse Human Tumor Cell Lines

Zhao

Zheng

Robbins

et al. 2005

The Journal of Immunology

Self Cite

182

162

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“…14,19 These positive serum samples were diluted at various concentrations and applied to ELISA plates coated with 12 candidate peptides consisting of 20 amino acid residues that span the entire surface-exposed domain of NY-ESO-1. As shown in Table I, and ESO:56-75, was also observed in 1 and 3 patients, respectively.…”

Section: Identification Of Ny-eso-1-derived B-cell Epitopes Recognizementioning

confidence: 99%

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

Zeng

Aldridge

Wang

et al. 2004

Intl Journal of Cancer

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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...

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“…Immunity to melanoma T Ramirez-Montagut et al epitopes (Jager et al, 2000;Zeng et al, 2000). It is one of the most immunogenic antigens known thus far.…”

Section: Cd4+cellsmentioning

confidence: 99%

Immunity to melanoma: unraveling the relation of tumor immunity and autoimmunity

et al. 2003

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Identification of CD4+ T Cell Epitopes from NY-ESO-1 Presented by HLA-DR Molecules

Cited by 128 publications

References 41 publications

Primary Human Lymphocytes Transduced with NY-ESO-1 Antigen-Specific TCR Genes Recognize and Kill Diverse Human Tumor Cell Lines

Primary Human Lymphocytes Transduced with NY-ESO-1 Antigen-Specific TCR Genes Recognize and Kill Diverse Human Tumor Cell Lines

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

Immunity to melanoma: unraveling the relation of tumor immunity and autoimmunity

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