Therapeutic Dendritic Cell Vaccination of Patients With Metastatic Renal Cell Carcinoma

Berntsen, Annika; Trepiakas, Redas; Wenandy, Lynn; Geertsen, Poul F.; Straten, Per thor; Andersen, Mads Hald; Pedersen, Anders Elm; Claësson, Mogens H.; Lorentzen, T.; Johansen, Julia S.; Svane, Inge Marie

doi:10.1097/cji.0b013e3181833818

Cited by 89 publications

(67 citation statements)

References 43 publications

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“…This study showed positive immune responses in 10 of 14 patients, along with anecdotal clinical responses [67]. DC loaded with both survivin and telomerase peptides have been tested in renal carcinoma where 13 of 27 patients experienced disease stabilization for 8 weeks along with 1 patient who had stable disease for 6 months [68,69]. In another study, DC pulsed with survivin and MAGE3 mRNA produced vaccinespecific CD3+ T cell production in multiple myeloma patients [70].…”

Section: Survivin Vaccines In Clinical Studiesmentioning

confidence: 72%

Survivin as a Cancer Vaccine Target

Ciesielski

Qiu²,

Fenstermaker³

2014

J Vaccines Vaccin

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Survivin expression is associated with a poor prognosis in many cancers. While survivin is being studied as a potentially important target for cancer therapy, its many biological functions in both normal and cancerous cells remain to be fully elucidated. There are at least six specific survivin splice variants that have been identified to date which appear to be self-regulating and may have distinct functions. Several survivin peptide vaccines are currently under development by different groups. Survivin vaccine strategies for the most part have focused upon particular regional epitopes of the molecule that are bound by MHC class I and can lead to a cytotoxic T cell response. Immunotherapy targeting survivin is still at an early stage of development; however, several agents are progressing through early phase clinical trials. Recent studies using SurVaxM, a multi-epitope cryptic peptide, survivin, mimic show specific CD8+ T cell responses, as well as specific CD4+ T cell stimulation. Currently SurVaxM is in Phase I clinical trials designed to study its safety, tolerability and immunological effects in patients with survivin-positive recurrent malignant gliomas and multiple myeloma.Keywords: Survivin; Immunotherapy; Peptide; Vaccine; Apoptosis SurvivinSurvivin is an 16.5 kDa intracellular protein that mediates a number of anti-apoptotic and oncogenic effects [1]. Survivin belongs to the inhibitor of apoptosis protein (IAP) family [2,3]. It acts in concert with the mitotic spindle apparatus to regulate cell division [4] and localizes to the spindle microtubule organizing center (MTOC) during the G2/M phase of the cell cycle [2,3,5]. Survivin has also been shown to modulate the function of a number of terminal effector cell death proteases (caspases) leading to an inhibition of apoptosis [3,[6][7][8]. Survivin expression is associated with a poor prognosis in many cancers [9,10]. While survivin is being studied as a potentially important target for cancer therapy, its many biological functions in both normal and cancerous cells remain to be fully elucidated.Survivin appears to function mainly as an anti-apoptotic molecule and its ability to interfere with p53 is one of its most studied molecular action [11][12][13]. However, the presence of survivin in the nucleus [14]; its interaction with the mitotic spindle [5]; its secondary localization inside mitochondria [15]; its presence in exosomes in plasma [16] observed exosomal release [17]; and the existence of circulating survivin-encoding mRNA [18,19]; and the existence of a many alternative mRNA splice variants all paint a complex picture of the molecule's possible actions. Although expressed during fetal development [1], survivin is rarely detectable in the normal tissues of adult organisms [20]. The cells of many different forms of cancer express survivin [1] and in some cases expression is related to tumor grade [9,10,21]. Survivin expression in tumors is associated with a high rate of disease recurrence and resistance to therapy, and it confers signific...

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Section: Survivin Vaccines In Clinical Studiesmentioning

confidence: 72%

Survivin as a Cancer Vaccine Target

Ciesielski

Qiu²,

Fenstermaker³

2014

J Vaccines Vaccin

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“…Berntsen and coworkers reported serum YKL-40 to associate with poor prognosis in patients with metastatic RCC treated with experimental dendritic cell vaccination therapy; YKL-40 levels increased significantly within the first four weeks of the treatment, with higher increase being in patients with progressive disease [18].…”

Section: Discussionmentioning

confidence: 99%

High YKL-40 is associated with poor survival in patients with renal cell carcinoma: a novel independent prognostic marker

Väänänen

Kallio

Vuolteenaho

et al. 2017

Scandinavian Journal of Urology

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Objective: YKL-40 is an inflammation-associated glycoprotein supposed to have a role in cell survival and angiogenesis. RCC is characterized by varying prognosis and risk of relapse after disease free time of years. Prognostic markers are critically needed. We investigated if YKL-40 could serve as a useful biomarker in RCC patients. Materials and Methods: Blood samples from 82 patients with RCC were collected at the time of diagnosis and 3, 5, and 9 months and 2 and 3 years after nephrectomy. Levels of YKL-40 were determined by ELISA. Survival of patients and relapse of RCC was followed up to 15 years.Results: Circulating YKL-40 levels were increased in patients with metastatic RCC at the time of diagnosis (115.7, 61.0-221.6 ng/ml; median, IQR). More importantly, among patients primarily diagnosed to have nonmetastatic RCC, baseline YKL-40 levels were significantly higher in those patients who experienced a relapse during the follow-up (103.7, 59.3-242.0 ng/ml) than in patients without relapse (50.6, 33.8-97.1 ng/ml). Moreover, high baseline YKL-40 was highly associated with poor prognosis in RCC: in age-adjusted univariate analysis, YKL-40 over 120 ng/ml (highest tertile) predicted over 5-fold mortality in 5 years, and in multivariate analysis high YKL-40 stayed as a statistically significant independent risk factor for 5 and 15 years survival. Conclusions:Increased circulating YKL-40 levels were found to be significantly associated with poor survival in patients with RCC. The results suggest YKL-40 as a useful novel biomarker in evaluating prognosis and relapse risk in RCC, being especially beneficial in patients primarily diagnosed to have nonmetastatic RCC.

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“…Head and neck [18,22,62] Lung cancer (small cell carcinoma) Lung [133,134] Breast cancer Breast Colorectal cancer Colon [20,132] Kidney tumor Kidney [132,142,143] Hepatocellular carcinoma Liver [21,66] Ovarian tumor, endometrial cancer Ovary [55][56][57][58][59][60][61]133,138,139] Primary prostate cancer Prostate [23,63,144] Metastatic prostate cancer Papilloma thyroid carcinoma, thyroid tumor Thyroid [136,145] Extracellular myxoidchondrosarcoma Bone [146] Multiple myeloma Bone marrow [147,148] Hodgkin's lymphoma Lymph node [65] Malignant melanoma Melanocyte [18,64] Myxoid liposarcoma Fat cells [146] 5252 ISSN 1007-9327 CN 14-1219/R World J Gastroenterol November 14, 2009 Volume 15 Number 42…”

Section: Glioma Oligodendroglioma Glioblastomamentioning

confidence: 99%

Potential role of chitinase 3-like-1 in inﬂammationassociated carcinogenic changes of epithelial cells

Eurich¹,

Segawa²,

Toei-Shimizu³

et al. 2009

WJG

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The family of mammalian chitinases includes members both with and without glycohydrolase enzymatic activity against chitin, a polymer of N-acetylglucosamine. Chitin is the structural component of fungi, crustaceans, insects and parasitic nematodes, but is completely absent in mammals. Exposure to antigens containing chitin-or chitin-like structures sometimes induces strong T helper type-I responses in mammals, which may be associated with the induction of mammalian chitinases. Chitinase 3-like-1 (CHI3L1), a member of the mammalian chitinase family, is induced specifically during the course of inflammation in such disorders as inflammatory bowel disease, hepatitis and asthma. In addition, CHI3L1 is expressed and secreted by several types of solid tumors including glioblastoma, colon cancer, breast cancer and malignant melanoma. Although the exact function of CHI3L1 in inflammation and cancer is still largely unknown, CHI3L1 plays a pivotal role in exacerbating the inflammatory processes and in promoting angiogenesis and remodeling of the extracellular matrix. CHI3L1 may be highly involved in the chronic engagement of inflammation which potentiates development of epithelial tumorigenesis presumably by activating the mitogen-activated protein kinase and the protein kinase B signaling pathways. Anti-CHI3L1 antibodies or pan-chitinase inhibitors may have the potential to suppress CHI3L1-mediated chronic inflammation and the subsequent carcinogenic change in epithelial cells.

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Therapeutic Dendritic Cell Vaccination of Patients With Metastatic Renal Cell Carcinoma

Cited by 89 publications

References 43 publications

Survivin as a Cancer Vaccine Target

Survivin as a Cancer Vaccine Target

High YKL-40 is associated with poor survival in patients with renal cell carcinoma: a novel independent prognostic marker

Potential role of chitinase 3-like-1 in inﬂammationassociated carcinogenic changes of epithelial cells

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