Chemotherapies and immunotherapies for metastatic kidney cancer

Ko, Yu Chieh; Atkins, Michael B.

doi:10.1007/s11934-005-0065-7

Cited by 6 publications

(3 citation statements)

References 47 publications

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“…Critical to the design of efficacious tumor vaccines, is achieving the optimal balance between both regulatory and effector T cell functions that results in the induction and maintenance of responses against tumor antigen(s). The careful timing of administration of both cytotoxic chemotherapy and immunotherapy agents may well be crucial to the success of such combined therapeutic ap-Vaccinated with MVA-5T4 (TroVax) Administered Alongside Two Different Chemotherapy Regimens proaches [27][28][29]. It could be possible to further optimize the timing of vaccination during the period that a patient receives chemotherapy through a more exquisite analysis of Treg numbers after each chemotherapy cycle.…”

Section: Discussionmentioning

confidence: 99%

Comparative Kinetics of Immune Responses and Changes in Cellular Sub-Sets Detected in Colorectal Cancer Patients Vaccinated with MVA-5T4 (TroVax) Administered Alongside Two Different Chemotherapy Regimens

Kelleher¹,

Shingler²,

Hawkins³

et al. 2011

JCT

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Modified vaccinia Ankara (MVA) virus encoding the tumor antigen 5T4 (MVA-5T4; TroVax?) has been tested in two open-label phase II studies in metastatic colorectal cancer patients alongside two chemotherapy regimens, 5-fluorouracil, folinic acid and irinotecan (IrMdG) or 5-fluorouracil, folinic acid and oxaliplatin (OxMdG). The aim of this study was to investigate the kinetics of immune responses and changes in cellular sub-sets before, during and after treatment with each chemotherapy regimen. In total, 23 patients received the complete course of treatment which comprised 2 injections before, during and after completion of chemotherapy. Antibody and cellular responses specific for 5T4 and MVA were monitored throughout the study and changes in immune cell subsets were determined. All 23 evaluable patients mounted MVA- and 5T4-specific cellular and/or humoral responses. Patients on both trials showed significant reductions in the numbers of neutrophils and the proportion of regulatory T cells (Treg) within the CD4+ T cell population. Monocyte and NK cell numbers decreased significantly in patients treated with IrMdG but not OxMdG. The largest increase in 5T4-specific cellular responses was observed 2 weeks following the completion of chemotherapy which was coincident with a decrease in Treg levels. Both chemotherapy regimens resulted in a significant decrease in the proportion of peripheral Tregs. Levels of Tregs during chemotherapy showed an inverse correlation with 5T4 cellular responses detected immediately post-chemotherapy. These data may support a rationale for sequencing chemotherapy with immunotherapy strategies at time points when Treg levels are predicted to be low

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Section: Discussionmentioning

confidence: 99%

Comparative Kinetics of Immune Responses and Changes in Cellular Sub-Sets Detected in Colorectal Cancer Patients Vaccinated with MVA-5T4 (TroVax) Administered Alongside Two Different Chemotherapy Regimens

Kelleher¹,

Shingler²,

Hawkins³

et al. 2011

JCT

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“…Epigenetic level control, such as methylation, may represent an additional mechanism since a strict correlation exists between demethylation and enhancements in STAT-1 phosphorylation followed by an increase in ISG expression [39]. From the gene ontology analysis it was interesting to observe the participation of hypoxia pathways in cancer cells with the "anti-viral" state as this can clearly affect tumor biology and responsiveness to chemotherapy [40] and likely immunotherapy of immune responsive cancers such as renal cell carcinoma [41] and melanoma [42]. …”

Section: Discussionmentioning

confidence: 99%

Anti-viral state segregates two molecular phenotypes of pancreatic adenocarcinoma: potential relevance for adenoviral gene therapy

et al. 2010

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BackgroundPancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer mortality for which novel gene therapy approaches relying on tumor-tropic adenoviruses are being tested.MethodsWe obtained the global transcriptional profiling of primary PDAC using RNA from eight xenografted primary PDAC, three primary PDAC bulk tissues, three chronic pancreatitis and three normal pancreatic tissues. The Affymetrix GeneChip HG-U133A was used. The results of the expression profiles were validated applying immunohistochemical and western blot analysis on a set of 34 primary PDAC and 10 established PDAC cell lines. Permissivity to viral vectors used for gene therapy, Adenovirus 5 and Adeno-Associated Viruses 5 and 6, was assessed on PDAC cell lines.ResultsThe analysis of the expression profiles allowed the identification of two clearly distinguishable phenotypes according to the expression of interferon-stimulated genes. The two phenotypes could be readily recognized by immunohistochemical detection of the Myxovirus-resistance A protein, whose expression reflects the activation of interferon dependent pathways. The two molecular phenotypes discovered in primary carcinomas were also observed among established pancreatic adenocarcinoma cell lines, suggesting that these phenotypes are an intrinsic characteristic of cancer cells independent of their interaction with the host's microenvironment. The two pancreatic cancer phenotypes are characterized by different permissivity to viral vectors used for gene therapy, as cell lines expressing interferon stimulated genes resisted to Adenovirus 5 mediated lysis in vitro. Similar results were observed when cells were transduced with Adeno-Associated Viruses 5 and 6.ConclusionOur study identified two molecular phenotypes of pancreatic cancer, characterized by a differential expression of interferon-stimulated genes and easily recognized by the expression of the Myxovirus-resistance A protein. We suggest that the detection of these two phenotypes might help the selection of patients enrolled in virally-mediated gene therapy trials.

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“…Among urologic malignancies, renal cell carcinoma (RCC) is particularly difficult to treat because one third of the patients diagnosed with RCC present with metastases and the advanced RCC responds poorly to conventional treatments such as chemotherapy or radiotherapy (Skinner et al, 1971;Leibovich et al, 2003). As an alternative approach to RCC treatment, immunotherapy, including cytokine therapy using interferon-(IFN-) or interleukin-2 (IL-2), has been introduced and produces response rates of 15-20% (Bukowski, 2000;Ko and Atkins, 2005). In view of the non-specific character of cytokine therapy, dendritic cell (DC)-based immunotherapy elicits more specific immune responses against tumors and has been shown to have therapeutic potential for treating RCC (Bleumer et al, 2007;Lim et al, 2007;Driessens et al, 2009).…”

mentioning

confidence: 99%

Immunostimulatory Activity of Dendritic cells pulsed with carbonic anhydrase IX and Acinetobacter baumannii outer membrane protein A

et al. 2011

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Dendritic cell (DC)-based immunotherapy is a potent therapeutic modality for treating renal cell carcinoma (RCC), but development of antigens specific for tumor-targeting and anti-tumor immunity is of great interest for clinical trials. The present study investigated the ability of DCs pulsed with a combination of carbonic anhydrase IX (CA9) as an RCC-specific biomarker and Acinetobacter baumannii outer membrane protein A (AbOmpA) as an immunoadjuvant to induce anti-tumor immunity against murine renal cell carcinoma (RENCA) in a murine model. Murine bone-marrow-derived DCs pulsed with a combination of RENCA lysates and AbOmpA were tested for their capacity to induce DC maturation and T cell responses in vitro. A combination of RENCA lysates and AbOmpA up-regulated the surface expression of co-stimulatory molecules, CD80 and CD86, and the antigen presenting molecules, major histocompatibility (MHC) class I and class II, in DCs. A combination of RENCA lysates and AbOmpA also induced interleukin-12 (IL-12) production in DCs. Next, the immunostimulatory activity of DCs pulsed with a combination of CA9 and AbOmpA was determined. A combination of CA9 and AbOmpA up-regulated the surface expression of co-stimulatory molecules and antigen presenting molecules in DCs. DCs pulsed with a combination of CA9 and AbOmpA effectively secreted IL-12 but not IL-10. These cells interacted with T cells and formed clusters. DCs pulsed with CA9 and AbOmpA elicited the secretion of interferon-γ and IL-2 in T cells. In conclusion, a combination of CA9 and AbOmpA enhanced the immunostimulatory activity of DCs, which may effectively induce anti-tumor immunity against human RCC.

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Chemotherapies and immunotherapies for metastatic kidney cancer

Cited by 6 publications

References 47 publications

Comparative Kinetics of Immune Responses and Changes in Cellular Sub-Sets Detected in Colorectal Cancer Patients Vaccinated with MVA-5T4 (TroVax) Administered Alongside Two Different Chemotherapy Regimens

Comparative Kinetics of Immune Responses and Changes in Cellular Sub-Sets Detected in Colorectal Cancer Patients Vaccinated with MVA-5T4 (TroVax) Administered Alongside Two Different Chemotherapy Regimens

Anti-viral state segregates two molecular phenotypes of pancreatic adenocarcinoma: potential relevance for adenoviral gene therapy

Immunostimulatory Activity of Dendritic cells pulsed with carbonic anhydrase IX and Acinetobacter baumannii outer membrane protein A

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