Identification of renal-cell-carcinoma-related cDNA clones by suppression subtractive hybridization

Pitzer, Claudia; Stassar, Marike; Zöller, Margot

doi:10.1007/s004320050306

Cited by 17 publications

(12 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…36,[39][40][41][42]45 So far, few RCC-associated antigens are known and have been clinically evaluated. 46,[48][49][50][51] We discovered by SSH that MAGE-9, originally described by De Plaen et al, 73 is also expressed in RCC 52 and have explored here its potential as an additional therapeutic target for RCC. The well-known RCC-associated RAGE-1 [53][54][55] served as a reference antigen.…”

Section: Discussionmentioning

confidence: 99%

“…52 Because only a limited number of immunotherapeutic targets for RCC are known, it became of interest to evaluate the frequency of MAGE-9 expression in RCC and its possible suitability as an immunogenic target. The expression profile of RAGE-1 in RCC is well known, and there are several reports on its immunogenicity.…”

Section: Mage-9 and Rage-1 Expression In Human Rccmentioning

confidence: 99%

“…[48][49][50][51] We previously observed, by SSH, expression of MAGE-9 in RCC. 52 As RAGE-1 has been described as an immunogenic RCC-associated antigen, [53][54][55] we explored the frequency of MAGE-9 expression in RCC and identified HLA-A*0201-restricted immunogenic MAGE-9 peptides in comparison to RAGE-1. We also report on the efficacy of B cells in peptide presentation and stimulation of peptide-specific CTLs.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Generation of RAGE‐1 and MAGE‐9 peptide‐specific cytotoxic T‐Lymphocyte lines for transfer in patients with renal cell carcinoma

Oehlrich

Devitt

Linnebacher

et al. 2005

Intl Journal of Cancer

View full text Add to dashboard Cite

Renal cell carcinomas (RCCs) are supposed to be immunogenic, and several clinical trials of immunotherapy using tumor lysatepulsed dendritic cells (DCs) have been performed. We report on the generation of RAGE-1 and MAGE-9 peptide-specific CTL lines. RAGE-1 and MAGE-9 are expressed in 56% and 38% of RCCs. Seven MAGE-9-and 13 RAGE-1-derived peptides were found to be immunogenic in the context of the HLA-A*0201 MHC. CTLs were generated by coculture with peptide-pulsed, activated B cells, which were easily generated in great quantities and displayed functional activity for a prolonged period of time. MAGE-9 and RAGE-1 peptide-specific CTL lines were strictly peptide-specific and displayed high cytotoxic activity not only against peptide-loaded T2 cells but also against HLA-A*0201-positive RCC lines, which naturally express MAGE-9, RAGE-1 or both. Thus, B cells are well suited as APCs for the generation of large numbers of tumor peptide-specific CTLs for adoptive transfer. MAGE-9 as well as RAGE-1 may well provide suitable targets for immunotherapy of RCC. ' 2005 Wiley-Liss, Inc.Key words: human renal cell carcinoma; antigen-presenting cell; peptide-specific cytotoxic T lymphocyte With 1-2% of solid tumors, RCCs are less frequent than prostate and bladder carcinomas.1 However, the prognosis of patients with RCC is poor as one-third of patients already have metastatic disease at the initial presentation and 30-40% develop distant metastases after resection of the primary tumor.2,3 Median survival time of metastatic RCC is only 6-8 months, and the 5-year survival rate is <5%. As >80% of RCCs express the phenotype of multidrug resistance, chemotherapy is rarely efficient. [4][5][6] However, RCCs are supposed to be immunogenic; 7-11 hence, immunotherapeutic strategies are dominant. should be mentioned. The antibody becomes internalized, 32 and application of 125 I-coupled G250 has been reported to retard tumor progression. 33-35Cell-mediated immunotherapeutic protocols in RCC have been based on tumor lysate-loaded DCs.36-39 Vaccination-induced remissions and an increase in the 5-year survival rate to 70% have been observed. [40][41][42] Application of tumor antigen cDNA 43 or of DC transduced with tumor antigen mRNA or cDNA 44,45 has been reported also to improve survival time, albeit to a minor degree. For antigen-specific vaccination in RCC, 46,47 so far MUC1, HSP96 and MN/CAIX have been used. Yet, the therapeutic efficacy remains below expectation. [48][49][50][51] We previously observed, by SSH, expression of MAGE-9 in RCC.52 As RAGE-1 has been described as an immunogenic RCC-associated antigen, [53][54][55] we explored the frequency of MAGE-9 expression in RCC and identified HLA-A*0201-restricted immunogenic MAGE-9 peptides in comparison to RAGE-1. We also report on the efficacy of B cells in peptide presentation and stimulation of peptide-specific CTLs. Material and methods Tumor linesHuman RCC lines 769-p, 56 Caki-1 and Caki-2, 57 ACHN, KTCTL-28, KTCTL-30, KTCTL-53 and KTCTL-111 (tumor bank,

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Mage-9 and Rage-1 Expression In Human Rccmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Generation of RAGE‐1 and MAGE‐9 peptide‐specific cytotoxic T‐Lymphocyte lines for transfer in patients with renal cell carcinoma

Oehlrich

Devitt

Linnebacher

et al. 2005

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…The fact that SSH and cDNA array analysis both showed a false positive rate of approximately 50% illustrates the point that all of the techniques used to identify differentially regulated genes must be confirmed by Northern blot hybridization to the original samples. The same RCC tissue (T9) was analysed by differential display RT-PCR in a previous study (Stassar et al, 1999). As compared to differential display RT-PCR, SSH yielded a higher number of differentially expressed genes and the rate of false positives was significantly lower.…”

Section: Discussionmentioning

confidence: 99%

True

2001

Br J Cancer

View full text Add to dashboard Cite

Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and 1.4% of cancer-related deaths (Reis and Faria, 1994). The prognosis of RCC remains poor. One third of the patients already have metastases when first consulting the hospital. Another 30-40% of patients develop metastases after surgical excision of the primary tumour (Ravaud and Debled, 1999). RCC are radioresistant (Nieder et al, 1996) and more than 80% are chemoresistant (Mickisch, 1994). Since RCC are presumed to be immunogenic, several clinical trials are exploring the efficacy of cytokines, mainly interleukin 2 (IL2) and/or interferon-α (IFNα), and the transfer of lymphokine-activated killer cells (Hofmockel et al, 1997;Bukowski, 2000;Hoffman et al, 2000). Despite these new options, the median survival time of patients with metastatic disease still remains only 6-8 months and the overall 5-year survival rate is less than 5% (Moch et al, 2000;Motzer and Russo, 2000). Thus, there is an urgent requirement for alternative therapeutic modalities.The current strategy is to design therapeutic approaches based on specific biological features of each tumour type. These include (i) the aberrant expression of genes which can be recognized by the immune system as foreign (Pawelec et al, 1999;Wang and Rosenberg, 1999;Bremers and Parmiani, 2000); (ii) gene products related to the formation of new blood vessels (neoangiogenesis), since they are essential for tumour expansion and metastatic settlement (Harris and Thorgeirsson, 1998;Kerbel, 2000;Rosen, 2000) and (iii) the altered expression of adhesion molecules, matrix-degrading enzymes, their receptors and inhibitors, which are a further requisite of metastatic spread (Huang et al, 1997;Yu et al, 1997).Several technique enable the identification of tumour markers. Subtractive hybridization (Lamar and Palmer, 1984; Kunkel et al, 1985;Kuang et al, 1998), differential display reverse transcription-polymerase chain reaction (DD RT-PCR; Liang and Pardee, 1992) and hybridization of cDNA microarrays (reviewed in Khan et al, 1999) are frequently used to compare the expression patterns between tumour and normal tissue. Other approaches, such as serological screening (SEREX;Sahin et al, 1995) and screening of cytotoxic T lymphocyte activity against an autologous tumour cell line (De Plaen et al, 1988), are especially focused on the identification of immunogenic tumour molecules.We have described recently the successful use of SSH using matched RCC and normal kidney tissue . In this study, we randomly selected 16 genes, which by SSH appeared to be differentially expressed. Differential expression of 9 of these 16 genes could be verified by Northern blot analysis. 2 of the 9 genes appeared to be novel. From the remaining 7 genes, expression of 5 had been associated with the malignant phenotype. To substantiate that SSH is a suitable method for the identification of differentially expressed genes, we performed a SSH with an additional pair of normal renal and RCC tissue and compared the validity of SSH ...

show abstract

“…Trying to expand the available panel of renal cell carcinoma (RCC) Ags, we recently identified by suppression subtractive hybridization MAGE-A9 (MAGE9), which is expressed in roughly one third of RCCs (31,32). We and other groups also noted that the majority of Ags identified by SEREX are autoantigens, which might be due to the liberation of cytoplasmic proteins during necrotic cell death that frequently occurs during tumor growth (32)(33)(34)(35).…”

mentioning

confidence: 99%

Concomitant Tumor and Autoantigen Vaccination Supports Renal Cell Carcinoma Rejection

Herbert

Haferkamp²,

Schmitz‐Winnenthal³

et al. 2010

The Journal of Immunology

View full text Add to dashboard Cite

Efficient tumor vaccination frequently requires adjuvant. Concomitant induction of an autoimmune response is discussed as a means to strengthen a weak tumor Ag-specific response. We asked whether the efficacy of dendritic cell (DC) vaccination with the renal cell carcinoma Ags MAGE-A9 (MAGE9) and G250 could be strengthened by covaccination with the renal cell carcinoma autoantigen GOLGA4. BALB/c mice were vaccinated with DC loaded with MHC class I-binding peptides of MAGE9 or G250 or tumor lysate, which sufficed for rejection of low-dose RENCA-MAGE9 and RENCA-G250 tumor grafts, but only retarded tumor growth at 200 times the tumor dose at which 100% of animals will develop a tumor. Instead, 75–100% of mice prevaccinated concomitantly with Salmonella typhimurium transformed with GOLGA4 cDNA in a eukaryotic expression vector rejected 200 times the tumor dose at which 100% of animals will develop tumor. In a therapeutic setting, the survival rate increased from 20–40% by covaccination with S. typhimurium-GOLGA4. Autoantigen covaccination significantly strengthened tumor Ag-specific CD4+ and CD8+ T cell expansion, particularly in peptide-loaded DC-vaccinated mice. Covaccination was accompanied by an increase in inflammatory cytokines, boosted IL-12 and IFN-γ expression, and promoted a high tumor Ag-specific CTL response. Concomitant autoantigen vaccination also supported CCR6, CXCR3, and CXCR4 upregulation and T cell recruitment into the tumor. It did not affect regulatory T cells, but slightly increased myeloid-derived suppressor cells. Thus, tumor cell eradication was efficiently strengthened by concomitant induction of an immune response against a tumor Ag and an autoantigen expressed by the tumor cell. Activation of autoantigen-specific Th cells strongly supports tumor-specific Th cells and thereby CTL activation.

show abstract

Identification of renal-cell-carcinoma-related cDNA clones by suppression subtractive hybridization

Cited by 17 publications

References 27 publications

Generation of RAGE‐1 and MAGE‐9 peptide‐specific cytotoxic T‐Lymphocyte lines for transfer in patients with renal cell carcinoma

Generation of RAGE‐1 and MAGE‐9 peptide‐specific cytotoxic T‐Lymphocyte lines for transfer in patients with renal cell carcinoma

True

Concomitant Tumor and Autoantigen Vaccination Supports Renal Cell Carcinoma Rejection

Contact Info

Product

Resources

About