Identification of HLA-A*0201-restricted CTL epitopes encoded by the tumor-specificMAGE-2 gene product

Visseren, M. J. W.; Burg, Sjoerd H. van der; Voort, Ellen I. H. van der; Brandt, R. M. P.; Schrier, Peter I.; Bruggen, Pierre van der; Boon, Thierry; Melief, Cornelis J.M.; Kast, W. Martin

doi:10.1002/(sici)1097-0215(19970926)73:1<125::aid-ijc19>3.0.co;2-f

Cited by 51 publications

(19 citation statements)

References 22 publications

(19 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The list of tumor antigens, recognized by T cells, is growing in number of antigens and in the type of tumor cells expressing them. Among this group, many specific antigens were identified, such as NY-ESO-1 and the MAGE-1 antigens, which belong to cancer-testis family, gp100, which belongs to the differentiation antigens group, and many more (Visseren et al, 1997;Chen et al, 1998a, b;Jager et al, 1998;Pascolo et al, 2001). It is well-established that human melanoma cells express antigens that are recognized by cytotoxic T-lymphocyte (CTL) derived from cancer patients (Brichard et al, 1993;Kawakami et al, 1994;Wolfel et al, 1994;Fleischhauer et al, 1996;Pittet et al, 1999;Kawakami et al, 2000;Engelhard et al, 2002;Romero et al, 2002;Schaed et al, 2002).…”

Section: T-cell Receptor-like Antibodiesmentioning

confidence: 99%

Novel antibodies as anticancer agents

2007

View full text Add to dashboard Cite

In recent years antibodies, whether generated by traditional hybridoma technology or by recombinant DNA strategies, have evolved from Paul Ehrlich's 'magic bullets' to a modern age 'guided missile'. In the recent years of immunologic research, we are witnessing development in the fields of antigen screening and protein engineering in order to create specific anticancer remedies. The developments in the field of recombinant DNA, protein engineering and cancer biology have let us gain insight into many cancer-related mechanisms. Moreover, novel techniques have facilitated tools allowing unique distinction between malignantly transformed cells, and regular ones. This understanding has paved the way for the rational design of a new age of pharmaceuticals: monoclonal antibodies and their fragments. Antibodies can select antigens on both a specific and a high-affinity account, and further implementation of these qualities is used to target cancer cells by specifically identifying exogenous antigens of cancer cell populations. The structure of the antibody provides plasticity resonating from its functional sites. This review will screen some of the many novel antibodies and antibody-based approaches that are being currently developed for clinical applications as the new generation of anticancer agents.

show abstract

Section: T-cell Receptor-like Antibodiesmentioning

confidence: 99%

Novel antibodies as anticancer agents

2007

View full text Add to dashboard Cite

show abstract

“…T2 cells were treated with 2 g/ml actinomycin D (Sigma, Zwijndrecht, The Netherlands) in IMDM ϩ 1% HS for 2 hr at 37°C to reduce the background release of IFN-␥ by CD8 ϩ cells upon incubation with T2 cells. After several washes, T2 cells were either not pulsed, pulsed with a single MART-1/Melan-A [27][28][29][30][31][32][33][34][35] 51 Cr-labeled T2 cells were pulsed with peptides at concentrations of 10 g/ml in IMDM for 30 min at 37°C, washed with HBBS, and resuspended in IMDM ϩ 5% FCS in the presence of a 50-fold excess of unlabeled K562 cells to block NK cell-mediated lysis. 10 3 labeled, peptide-loaded T2 target cells were seeded together with CD8…”

Section: Enzyme-linked Immunospot (Elispot) Assaymentioning

confidence: 99%

“…All peptides are described as human CTL epitopes, 8,24 -30 except for the MAGE-2 peptides, which have been demonstrated to be immunogenic in HLA-A*0201K b transgenic mice. 31 We screened nonstimulated as well as in vitro peptide-stimulated CD8 ϩ cells to investigate whether the ELISPOT assay allows direct ex vivo detection of antigen-specific T cells and whether the sensitivity of the assay can be further enhanced by in vitro stimulation. …”

mentioning

confidence: 99%

Detection and quantification of CD8+ T cells specific for HLA-A*0201-binding melanoma and viral peptides by the IFN-?-elispot assay

et al. 2001

Self Cite

View full text Add to dashboard Cite

Blood lymphocytes from HLA-A*0201-subtyped melanoma patients and healthy controls were screened for the presence of T cells specific for HLA-A*0201-binding melanoma and viral peptide antigens by the enzyme-linked immunoSPOT (ELISPOT) assay. CD8؉ cells were tested for peptide-specific IFN-␥ release immediately after selection as well as after 2 weeks of in vitro stimulation. After in vitro stimulation, CD8؉ T cells specific for influenza were measured in all patients and controls, whereas these T cells could be detected among nonstimulated CD8؉ cells in only 52% of individuals. Similarly, T cells specific for EBV were more frequently measured among in vitro-stimulated than nonstimulated CD8؉ cells. In nonstimulated CD8 ؉ cells, T cells specific for MART-1/Melan-A, gp100, tyrosinase and CAMEL were present in 4 (33%), 1 (8%), 1 (8%) and 3 (25%) of 12 patients, respectively. Only MART-1/Melan-A-specific CD8 ؉ T cells were found in 1 (11%) of 9 healthy controls. CD8؉ T cells specific for MAGE-2 were not observed. After in vitro stimulation, CD8؉ T cells specific for MART-1/Melan-A could be demonstrated in 6 (46%) of 13 patients and 2 (20%) of 10 controls. CD8 ؉ T cells specific for gp100 were detected in 1 patient after in vitro stimulation. No CD8 ؉ T cells specific for tyrosinase, MAGE-2 or CAMEL could be measured after in vitro stimulation. These data show that the ELISPOT assay allows direct ex vivo detection of CD8 ؉ T cells specific for viral and melanoma antigens. Furthermore, the data show that the sensitivity of the ELISPOT assay to measure influenza-and EBV-specific CD8 ؉ T cells can be enhanced by a short in vitro stimulation step, whereas opposing effects on numbers of CD8 ؉ T cells specific for melanoma antigens have been observed. © 2001 Wiley-Liss, Inc. Key words: human; blood; T lymphocytes; MHC; melanoma Cytotoxic CD8ϩ T lymphocytes (CTLs) play an important role in the host defense against many tumors by recognizing specific antigens as short peptides presented on the cell surface by MHC class I molecules. A number of genes coding for CTL epitopes have been identified and characterized in human melanoma. These genes have been isolated by screening cells transfected with cosmid or cDNA libraries for recognition by CTL clones or lines derived from peripheral blood or tumor-infiltrating lymphocytes. Some of these genes, e.g., MAGE, 1 BAGE 2 and GAGE, 3 encoding the so-called cancer-testis antigens, are frequently expressed in tumors of different origins but silent in normal tissues except for testis. Although expressed in other tumor types as well, MAGE genes are most frequently expressed in human melanoma. In particular MAGE-2 and -3 have been reported to be expressed in 30% to 40% of primary and 70% to 80% of metastatic melanoma. 4 -6 In addition to cancer-testis antigens, genes have been isolated coding for melanocyte differentiation antigens, e.g., MART-1/Melan-A, 7,8 tyrosinase, 9 gp100 8,10 and gp75. 11 Melanocyte differentiation antigens are expressed in a high percentage of primary and metastic...

show abstract

“…These epitopes, however, were all screened from nonamer libraries. Because CTL epitopes are also known to occur as decamers (33)(34)(35)(36)(37), the possible existence of decameric epitopes in SARSCoV remains to be explored. In addition, all three identified epitopes were localized in the S2 domain.…”

mentioning

confidence: 99%

Screening and Identification of Severe Acute Respiratory Syndrome-Associated Coronavirus-Specific CTL Epitopes

Zhou

De-sheng

et al. 2006

The Journal of Immunology

107

View full text Add to dashboard Cite

Severe acute respiratory syndrome (SARS) is a highly contagious and life-threatening disease that emerged in China in November 2002. A novel SARS-associated coronavirus was identified as its principal etiologic agent; however, the immunopathogenesis of SARS and the role of special CTLs in virus clearance are still largely uncharacterized. In this study, potential HLA-A*0201-restricted spike (S) and nucleocapsid protein-derived peptides were selected from an online database and screened for potential CTL epitopes by in vitro refolding and T2 cell-stabilization assays. The antigenicity of nine peptides which could refold with HLA-A*0201 molecules was assessed with an IFN-γ ELISPOT assay to determine the capacity to stimulate CTLs from PBMCs of HLA-A2+ SARS-recovered donors. A novel HLA-A*0201-restricted decameric epitope P15 (S411–420, KLPDDFMGCV) derived from the S protein was identified and found to localize within the angiotensin-converting enzyme 2 receptor-binding region of the S1 domain. P15 could significantly enhance the expression of HLA-A*0201 molecules on the T2 cell surface, stimulate IFN-γ-producing CTLs from the PBMCs of former SARS patients, and induce specific CTLs from P15-immunized HLA-A2.1 transgenic mice in vivo. Furthermore, significant P15-specific CTLs were induced from HLA-A2.1-transgenic mice immunized by a DNA vaccine encoding the S protein; suggesting that P15 was a naturally processed epitope. Thus, P15 may be a novel SARS-associated coronavirus-specific CTL epitope and a potential target for characterization of virus control mechanisms and evaluation of candidate SARS vaccines.

show abstract

Identification of HLA-A*0201-restricted CTL epitopes encoded by the tumor-specificMAGE-2 gene product

Cited by 51 publications

References 22 publications

Novel antibodies as anticancer agents

Novel antibodies as anticancer agents

Detection and quantification of CD8+ T cells specific for HLA-A*0201-binding melanoma and viral peptides by the IFN-?-elispot assay

Screening and Identification of Severe Acute Respiratory Syndrome-Associated Coronavirus-Specific CTL Epitopes

Contact Info

Product

Resources

About