Immunotherapy for Renal Cell Carcinoma

Bleumer, I.; Oosterwijk, Egbert; Mulder, Pieter De; Mulders, Peter F.A.

doi:10.1016/s0302-2838(03)00191-x

Cited by 106 publications

(71 citation statements)

References 80 publications

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“…More than 40% of patients diagnosed with metastatic disease are highly resistant to chemotherapy or radiotherapy (2). Immunotherapy with interferon -a (IFN-a) or interleukin -2 is available; however, it is effective in only a small minority of patients (3). Therefore, it is necessary to develop more effective chemotherapeutic modalities for RCC.…”

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confidence: 99%

Retinoic Acid and the Histone Deacetylase Inhibitor Trichostatin A Inhibit the Proliferation of Human Renal Cell Carcinoma in a Xenograft Tumor Model

Touma

Goldberg²,

Moench

et al. 2005

Clinical Cancer Research

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Purpose: Therapy for advanced renal cell carcinoma (RCC) is ineffective in the majority of patients.We have previously reported that retinoid-induced up-regulation of retinoic acid receptor h (RARh) correlated with antitumor effects in RCCs. Recent studies show that there is a reduction in the level of RARh 2 expression in cancer cells due in part to histone hypoacetylation. Therefore, we tested whether combining histone deacetylase inhibitors with retinoic acid (RA) would restore RARh 2 receptor expression, leading to increased growth inhibition in RCC cells. Experimental Design: Cell proliferation,Western blot, and reverse transcription-PCR analyses of two RA-resistant RCC cell lines, SK-RC-39 and SK-RC-45, were assessed in the presence of alltrans retinoic acid (ATRA), trichostatin A (TSA), or the combination of ATRA andTSA. Analysis of apoptosis was also done on SK-RC-39 cells treated with these combinations. Additionally, a xenograft tumor model (SK-RC-39) was used in this study to investigate the efficacy of a liposomeencapsulated, i.v. form of ATRA (ATRA-IV) plus TSA combination therapy. Results: Enhanced inhibition of the proliferation of RCC cell lines and of tumor growth in a xenograft model was observed with the combination of ATRA plus TSA. Reactivation of RARh 2 mRNA expression was observed in SK-RC-39 and SK-RC-45 cells treated with TSA alone or TSA in combination with ATRA. A partial G 0 -G 1 arrest and increased apoptosis were observed with SK-RC-39 cells on treatment with ATRA and TSA. Conclusions: The combination of ATRA and the histone deacetylase inhibitorTSA elicits an additive inhibition of cell proliferation in RCC cell lines. These results indicate that ATRA and histone deacetylase inhibitor therapies should be explored for the treatment of advanced RCC.

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confidence: 99%

Retinoic Acid and the Histone Deacetylase Inhibitor Trichostatin A Inhibit the Proliferation of Human Renal Cell Carcinoma in a Xenograft Tumor Model

Touma

Goldberg²,

Moench

et al. 2005

Clinical Cancer Research

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“…[1][2][3] Patients diagnosed with metastatic disease have a very poor prognosis because these tumors are commonly resistant to chemotherapy and radiotherapy. Immunotherapeutic treatment options are associated with very high toxicities and poor outcomes.…”

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confidence: 99%

“…Immunotherapeutic treatment options are associated with very high toxicities and poor outcomes. 1,2,4 The current classification system for RCC has a number of subtypes. 5 The two most common subtypes are conventional or clear cell RCC (ccRCC), representing approximately 70 -80% of patients, and papillary RCC (PRCC), which is reportedly observed in only 10 -15% of patients.…”

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Endothelin axis expression is markedly different in the two main subtypes of renal cell carcinoma

Douglas

Richardson

Nicol

2004

Cancer

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BACKGROUNDThe endothelin axis has been implicated in cancer growth, angiogenesis, and metastasis, but to the authors' knowledge the expression of endothelin genes has not been defined in renal cell carcinoma (RCC).METHODSTissue specimens were harvested from both normal and tumor‐affected regions at the time of radical nephrectomy from 35 patients with RCC (22 with clear cell RCC [ccRCC] and 13 with papillary RCC [PRCC]). Real‐time reverse transcriptase‐polymerase chain reaction analysis determined the expression profile of the preproendothelins (PPET‐1, PPET‐2, and PPET‐3), the endothelin receptors (ETA and ETB), and the endothelin‐converting enzymes (ECE‐1 and ECE‐2).RESULTSPPET‐1 was found to be up‐regulated in ccRCC tumor specimens and down‐regulated in PRCC tumor specimens. ETA was significantly down‐regulated in PRCC tumor specimens. ECE‐1 was expressed in all tissue specimens at comparable levels, with moderate but significant elevation in normal tissue specimens associated with PRCC. Of the other genes, PPET‐2 and ETB were expressed in all tissue specimens and no differences were observed between tumor subtypes or tumor‐affected and normal tissue specimens, whereas PPET‐3 and ECE‐2 were present in all tissue specimens but were barely detectable.CONCLUSIONSThe endothelin axis was expressed differently in the two main subtypes of RCC and appeared to match macroscopic features commonly observed in these tumors (i.e., high expression of PPET‐1 in hypervascular ccRCC contrasted against low PPET‐1 and ETA expression in hypovascular PRCC). The presence of ECE‐1 mRNA in these tissue specimens suggested that active endothelin ligands were present, indicating endothelin axis activity was elevated in ccRCC compared with normal kidney, but impaired in PRCC. The current study provided further evidence that it is not appropriate to consider ccRCC and PRCC indiscriminately in regard to treatment. Cancer 2004. © 2004 American Cancer Society.

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“…Simultaneously, RCC is not sensitive to radiotherapy and chemotherapy (3). Since RCC is a highly immunogenic tumor, advances in molecular and immune biology allow for the potential use of tumor vaccines as immune therapy (4).…”

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confidence: 99%

Construction of a fusion expression plasmid containing the G250 gene and human granulocyte-macrophage colony stimulating factor and its significance in renal cell carcinoma

Gong²,

Li³

et al. 2010

Oncology Letters

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Abstract. This study aimed to construct a eukaryotic expression plasmid containing the G250/MN/CA IX (G250) and human granulocyte-macrophage colony stimulating factor (hGM-CSF) genes, and to detect the expression of these proteins in vitro by recombinant plasmids in eukaryotic cells. pORF-hGM-CSF and pcDNA3.0-G250 were used as the template to amplify G250 and hGM-CSF by routine polymerase chain reaction (PCR). The two PCR products were cloned into the eukaryotic vector pVAX1, in order to construct a recombinant plasmid pVAX1-G250-hGM, and the plasmid was transfected into human embryonic kidney 293 cells. The protein expression was then determined by immunocytochemistry, atomic force microscopy, ELISA and Western blotting. DNA sequencing showed that the cloned G250 and hGM-CSF sequences were consistent with the reported Gene Bank ones. Moreover, a high expression was noted following recombinant plasmid transfection of the G250 and hGM-CSF proteins. Thus, the eukaryotic expression vector pVAX1-G250-hGM containing G250 and hGM-CSF was constructed, allowing for the investigation of the anti-G250 antigen vaccine and immune response mechanisms of biological immunotherapy in renal cell carcinoma. IntroductionRenal cell carcinoma (RCC) is a common malignant tumor of the urinary system. One out of nearly a million individuals succumb to the disease each year worldwide and the incidence is on the increase (1). RCC patients frequently present with subclinical disease and 20-30% of patients are admitted (2).However, traditional radical nephrectomy in RCC in the early stage has a positive effect, which is not the case in advanced stage and metastatic RCC. Simultaneously, RCC is not sensitive to radiotherapy and chemotherapy (3). Since RCC is a highly immunogenic tumor, advances in molecular and immune biology allow for the potential use of tumor vaccines as immune therapy (4). G250/MN/CA IX (MN antigen receptor/ carbonic anhydrase-9) is one of the tumor markers that possess favorable tumor specificity (5). The specific expression of G250/MN/CA IX in RCC renders it a key target for cancer diagnosis and treatment. In this study, a eukaryotic expression vector, containing the G250/MN/CA IX and human granulocyte-macrophage colony stimulating factor (hGM-CSF) genes, was constructed and transfected into human embryonic kidney 293 (HEK 293) cells. The fusion protein expression and immunoreactivity were then detected to establish anti-renal cell carcinoma vaccines for studies based on the G250 gene. Materials and methodsMaterials. E. coli Top 10, vector pVAX1, recombinant plasmid pORF-hGM-CSF and pcDNA3.0-G250 were obtained from

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Immunotherapy for Renal Cell Carcinoma

Cited by 106 publications

References 80 publications

Retinoic Acid and the Histone Deacetylase Inhibitor Trichostatin A Inhibit the Proliferation of Human Renal Cell Carcinoma in a Xenograft Tumor Model

Retinoic Acid and the Histone Deacetylase Inhibitor Trichostatin A Inhibit the Proliferation of Human Renal Cell Carcinoma in a Xenograft Tumor Model

Endothelin axis expression is markedly different in the two main subtypes of renal cell carcinoma

Construction of a fusion expression plasmid containing the G250 gene and human granulocyte-macrophage colony stimulating factor and its significance in renal cell carcinoma

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