Identification of multiple cancer/testis antigens by allogeneic antibody screening of a melanoma cell line library

Chen, Yao‐Tseng; Güre, Ali O.; Tsang, Solam; Stockert, Elisabeth; Jäger, Elke; Knuth, Alexander; Old, Lloyd J.

doi:10.1073/pnas.95.12.6919

Cited by 259 publications

(174 citation statements)

References 26 publications

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“…The potential of SEREX-defined CT antigens to induce cellular immunity despite a low frequency of antibodies in allogenic sera has been confirmed (Wang et al, 2002). The SEREX-defined NY-ESO-1 can induce a CTL response and the CTL-defined MAGEA-1 has also been identified by SEREX (Chen et al, 1998;Jager et al, 2000). This suggests that SEREX-cloned antigens may contain T-and B-cell epitopes.…”

Section: Discussionmentioning

confidence: 92%

Transduction of dendritic cells with recombinant adenovirus encoding HCA661 activates autologous cytotoxic T lymphocytes to target hepatoma cells

et al. 2004

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Transduction of recombinant adenovirus into dendritic cells (DCs) is a promising new tool for cancer vaccine development. Here, we report that an adenovirus vector carrying hepatocellular carcinoma (HCC) antigen HCA661 and infected into DCs generates T-cell immunity against hepatoma cells. HCA661 is a novel cancer/testis (CT) antigen screened by SEREX from sera of an HCC patient. We constructed a recombinant adenovirus expressing the full-length cDNA of HCA661 gene and then transduced immature DCs, which had been generated with GM-CSF and IL-4 from peripheral blood mononuclear cell of HLA-A2 þ healthy donors. The resulting adenovirus-transduced DCs differentiated in the presence of monocyte-conditioned medium and poly [I] : poly [C], expressing the surface markers of mature DCs, including CD83, CD80, CD86 and HLA-DR. After maturation, the transduced DCs transcribed HCA661 mRNA and were able to prime the naïve T cells to become cytotoxic T lymphocytes (CTLs). Intracellular flow cytometry and enzyme-linked immunospot assay showed that these CTLs were able to target a hepatoma cell line, HepG2, which is HLA-A2 and HCA661 positive. In summary, we found that this recombinant adenovirus can help to induce DC maturation and these mature DCs can activate T cells to target hepatoma cells. Therefore, this recombinant adenovirus may have potential for use in liver cancer immunotherapy.

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Section: Discussionmentioning

confidence: 92%

Transduction of dendritic cells with recombinant adenovirus encoding HCA661 activates autologous cytotoxic T lymphocytes to target hepatoma cells

et al. 2004

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“…The purpose of this truncation was to exclude the C-terminus, which shares significant homology with MAGE-A antigens. 10 Expression cloning into the plasmid vector pQE9, induction of recombinant protein synthesis and subsequent purification by Ni ϩ2 affinity chromatography were performed as described previously. 12,13 …”

Section: Production Of Recombinant Ct7 Proteinmentioning

confidence: 99%

“…Immunoblotting was done as previously described on recombinant CT7 protein and lysates of several cell lines, which were tested by RT-PCR for CT7 expression. 10,12 …”

Section: Generation Of An Anti-ct7 Monoclonal Antibodymentioning

confidence: 99%

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CT7 (MAGE‐C1) antigen expression in normal and neoplastic tissues

Jungbluth

Chen

Busam

et al. 2002

Intl Journal of Cancer

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CT7 (MAGE-C1) is a member of the cancer testis (CT)antigen family. The present study describes the generation of CT7-33, a monoclonal antibody (MAb) to CT7, and the preliminary protein expression analysis of CT7 in normal tissues and in a limited number of neoplastic lesions. CT7-33 was effective in frozen as well as formalin-fixed, paraffin-embedded tissues, and immunohistochemistry/reverse transcriptase polymerase chain reaction (RT-PCR) co-typing demonstrated antibody specificity. CT7-33 immunoreactivity in normal adult tissues is restricted to testicular germ cells. In neoplastic lesions, CT7-33 immunostaining is confined to tumor cells, and the frequency of CT7 protein expression mostly parallels previous mRNA analyses. Whereas colorectal and renal cell carcinomas, as well as sarcomas, exhibit poor or no CT7-33 staining, carcinomas of the mammary gland and ovary, nonsmall cell lung carcinoma and metastatic melanomas exhibit a high incidence of CT7 protein expression. However, as seen in previous analyses of other CT antigens, the expression pattern is mostly heterogeneous, and tumors with more than 50% of tumor staining are only infrequently encountered. In summary, our study Key words: CT7; MAGE-C1; heterogeneous antigen expression; monoclonal antibody CT7-33Cancer testis (CT) antigens are expressed in a variety of malignant neoplasms but not in normal adult tissues except for germ cells of the testis. 1,2 Due to their expression pattern, CT antigens appear to be ideal targets for immunotherapeutic strategies against malignant neoplasms. Since the isolation of the prototype CT gene family, MAGE, the number of CT antigens has steadily increased. 3 Whereas autologous T-cell epitope cloning was used for the initial identification of CT antigens such as MAGE and BAGE, 4,5 others have been isolated by SEREX (serological analysis of recombinant cDNA expression libraries) analysis. SEREX employs the immunologic screening of cDNA expression libraries from human tumors with autologous patient sera. 6 -9 By using the SEREX approach, we recently identified CT7, 10 a new member of the CT family. The same gene was isolated independently by Lucas et al. 11 using representational difference analysis (RDA) and termed MAGE-C1. A preliminary RT-PCR analysis revealed the presence of CT7 (MAGE-C1) in normal testis and in a variety of neoplasms, such as melanoma, and tumors of the urinary bladder, breast and lung. To assess CT7 as a potential target for immunotherapy, analysis of its actual antigen expression is essential. The present study describes the generation of the monoclonal antibody (MAb) CT7-33 to CT7 (MAGE-C1) and an immunohistochemical analysis of CT7 (MAGE-C1) expression in normal and tumorous tissues. MATERIAL AND METHODS Production of recombinant CT7 proteinA truncated CT7 product was chosen for the expression in E. coli. This truncated form encoded 350 of 1,124 amino acids in the CT7 antigen, namely positions 552-901. The purpose of this truncation was to exclude the C-terminus, which shares significant homolo...

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“…The method has enabled the discovery of several novel genes with tumour specificity, such as NY-ESO-1 , LAGE. (Lethe et al, 1998), SCP-1 (Türeci et al, 1998b), SSX (Türeci et al, 1996) and CT7 (Chen et al, 1998). These antigens are also expected to become new candidates for cancer-specific immunotherapy, but little information is available on the comprehensive expression of CTAs in a large number of samples of gastrointestinal and breast carcinomas.…”

Section: Introductionmentioning

confidence: 99%

Expression of multiple cancer-testis antigen genes in gastrointestinal and breast carcinomas

et al. 2001

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Summary Cancer-testis antigens (CTAs) such as MAGE are selectively expressed in various types of human neoplasms but not in normal tissues other than testis. This characteristic feature of CTAs makes them promising antigens for cancer-specific immunotherapy. A critical requirement for this therapy is identification of promising antigens. In this study, we investigated the expression of 6 genes recently identified by serological analysis of antigens by recombinant expression (SEREX) libraries: NY-ESO-1, LAGE-1, SCP-1, SSX-1, SSX-2, and SSX-4, in many surgical samples of gastrointestinal and breast carcinomas using reverse transcription-polymerase chain reaction. We found relatively high expression of SCP-1 (23.5%) and SSX-4 (20.6%) in gastric carcinoma, LAGE-1 (39.1%) and NY-ESO-1 (23.9%) in oesophageal carcinoma, and SCP-1 (34.1%) in breast carcinoma. We also found frequent synchronous expression with MAGE, including LAGE-1 (46.2%) in oesophageal carcinoma, SSX-4 (46.7%) in gastric carcinoma, and SCP-1 (38.3%) in breast carcinoma. Immunohistochemical analysis of the tumour samples expressing both MAGE-4 and NY-ESO-1 genes demonstrated differences in distribution between MAGE-4 and NY-ESO-1 in serial sections. We concluded that NY-ESO-1, LAGE-1, SCP-1 and SSX-4 genes may be promising candidates for cancer-specific immunotherapy in addition to MAGE, and that polyvalent cancer vaccines may be useful in cases of heterogeneous expressions of CTA genes in gastrointestinal and breast carcinomas.

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Identification of multiple cancer/testis antigens by allogeneic antibody screening of a melanoma cell line library

Cited by 259 publications

References 26 publications

Transduction of dendritic cells with recombinant adenovirus encoding HCA661 activates autologous cytotoxic T lymphocytes to target hepatoma cells

Transduction of dendritic cells with recombinant adenovirus encoding HCA661 activates autologous cytotoxic T lymphocytes to target hepatoma cells

CT7 (MAGE‐C1) antigen expression in normal and neoplastic tissues

Expression of multiple cancer-testis antigen genes in gastrointestinal and breast carcinomas

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