Tumor mRNA-transfected dendritic cells stimulate the generation of CTL that recognize neuroblastoma-associated antigens and kill tumor cells: immunotherapeutic implications.

Abstract:

:Several observations suggest a potential role of T-cell-mediated immunity in the control of neuroblastoma (NB). However, the generation of NB-specific cytotoxic T lymphocytes (CTL) on T-cell priming with tumor mRNA-transfected dendritic cells (DC) has never been investigated before. In the present study, the feasibility of this strategy has been analyzed, both in healthy donors and in NB patients. Monocyte-derived DC were raised from three human leukocyte antigen (HLA) A2+ NB patients and seven HLA-A1+ or HLA-A2+ healthy donors transfected with mRNA from four NB cell lines and cocultured with autologous CD8+ lymphocytes. Expanded CTL expressed an effector/memory phenotype and a T cytotoxic 1-like profile of cytokine secretion. CTL specificity was demonstrated by interferon-gamma release on incubation with HLA-matched NB cell lines. The latter cell lines, but not autologous T-cell blasts, were lysed by CTL in an HLA-restricted manner. Cytotoxicity was found to involve the release of granzyme B. When tested for reactivity against NB-associated antigens, CTL from normal individuals recognized anaplastic lymphoma-associated kinase (ALK) and preferentially expressed antigen of melanoma (PRAME) peptides only, whereas patients' CTL reacted also to survivin, telomerase, and tyrosine hydroxylase peptides. This study demonstrates that DC transfected with NB mRNA induce the generation of patients' CTL specific for different NB-associated antigens, supporting the feasibility of NB T-cell immunotherapy.

journal_name

Neoplasia

authors

Morandi F,Chiesa S,Bocca P,Millo E,Salis A,Solari M,Pistoia V,Prigione I

doi

10.1593/neo.06415

subject

Has Abstract

pub_date

2006-10-01 00:00:00

pages

833-42

issue

10

eissn

1522-8002

issn

1476-5586

journal_volume

8

pub_type

杂志文章
  • TGFBR2 mediated phosphorylation of BUB1 at Ser-318 is required for transforming growth factor-β signaling.

    abstract::BUB1 (budding uninhibited by benzimidazoles-1) is required for efficient TGF-β signaling, through its role in stabilizing the TGFBR1 and TGFBR2 complex. Here we demonstrate that TGFBR2 phosphorylates BUB1 at Serine-318, which is conserved in primates. S318 phosphorylation abrogates the interaction of BUB1 with TGFBR1 ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2020.02.001

    authors: Nyati S,Gregg BS,Xu J,Young G,Kimmel L,Nyati MK,Ray D,Speers C,Rehemtulla A

    更新日期:2020-04-01 00:00:00

  • A Pre-Clinical Assessment of the Pan-ERBB Inhibitor Dacomitinib in Pediatric and Adult Brain Tumors.

    abstract::Glioblastoma in adults, and medulloblastoma and pineoblastoma that mainly affect children, are aggressive brain tumors. The survival for patients with glioblastoma remains dismal. While the cure rate for medulloblastoma exceeds 70%, this figure has stagnated over the past few decades and survivors still contend with s...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2018.02.004

    authors: Endersby R,Whitehouse J,Hii H,Greenall SA,Johns TG,Gottardo NG

    更新日期:2018-05-01 00:00:00

  • Slit2 inhibits growth and metastasis of fibrosarcoma and squamous cell carcinoma.

    abstract::Slits are a group of secreted glycoproteins that play a role in the regulation of cell migration. Previous studies suggested that Slit2 might be a tumor-suppressor gene. However, it remained to be determined whether Slit2 suppressed tumor growth and metastasis in animal models. We showed that Slit2 expression was decr...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.08804

    authors: Kim HK,Zhang H,Li H,Wu TT,Swisher S,He D,Wu L,Xu J,Elmets CA,Athar M,Xu XC,Xu H

    更新日期:2008-12-01 00:00:00

  • PI3K/Akt pathway activation attenuates the cytotoxic effect of methyl jasmonate toward sarcoma cells.

    abstract::Methyl jasmonate (MJ) acts both in vitro and in vivo against various cancer cell lines. Activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway results in decreased susceptibility to cytotoxic agents in many types of cancer cells. We found a strong inverse correlation between the basal level of phospho-Akt ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.08636

    authors: Elia U,Flescher E

    更新日期:2008-11-01 00:00:00

  • Hepatitis B virus X protein inhibits tumor suppressor miR-205 through inducing hypermethylation of miR-205 promoter to enhance carcinogenesis.

    abstract::The infection of hepatitis B virus (HBV) is closely associated with the development of hepatocellular carcinoma (HCC), in which HBV X protein (HBx) plays crucial roles. MicroRNAs are involved in diverse biologic functions and in carcinogenesis by regulating gene expression. In the present study, we aim to investigate ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.131362

    authors: Zhang T,Zhang J,Cui M,Liu F,You X,Du Y,Gao Y,Zhang S,Lu Z,Ye L,Zhang X

    更新日期:2013-11-01 00:00:00

  • Current Evidence and Future Perspectives on HuR and Breast Cancer Development, Prognosis, and Treatment.

    abstract::Hu-antigen R (HuR) is an RNA-binding posttranscriptional regulator that belongs to the Hu/ELAV family. HuR expression levels are modulated by a variety of proteins, microRNAs, chemical compounds, or the microenvironment, and in turn, HuR affects mRNA stability and translation of various genes implicated in breast canc...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章,评审

    doi:10.1016/j.neo.2016.09.002

    authors: Kotta-Loizou I,Vasilopoulos SN,Coutts RH,Theocharis S

    更新日期:2016-11-01 00:00:00

  • Association of the actin-binding protein transgelin with lymph node metastasis in human colorectal cancer.

    abstract::Metastatic dissemination of primary tumors is responsible for 90% of colorectal cancer (CRC) deaths. The presence of positive lymph nodes, which separates stage I/II from stage III CRC, is a particularly key factor in patient management. Here, we describe results of a quantitative proteomic survey to identify molecula...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.09542

    authors: Lin Y,Buckhaults PJ,Lee JR,Xiong H,Farrell C,Podolsky RH,Schade RR,Dynan WS

    更新日期:2009-09-01 00:00:00

  • A pathologic link between Wilms tumor suppressor gene, WT1, and IFI16.

    abstract::The Wilms tumor gene (WT1) is mutated or deleted in patients with heredofamilial syndromes associated with the development of Wilms tumors, but is infrequently mutated in sporadic Wilms tumors. By comparing the microarray profiles of syndromic versus sporadic Wilms tumors and WT1-inducible Saos-2 osteosarcoma cells, w...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.07869

    authors: Kim MK,Mason JM,Li CM,Berkofsky-Fessler W,Jiang L,Choubey D,Grundy PE,Tycko B,Licht JD

    更新日期:2008-01-01 00:00:00

  • Microarray and biochemical analysis of lovastatin-induced apoptosis of squamous cell carcinomas.

    abstract::We recently identified 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme of the mevalonate pathway, as a potential therapeutic target of the head and neck squamous cell carcinomas (HNSCC) and cervical carcinomas (CC). The products of this complex biochemical pathway, including de novo...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900247

    authors: Dimitroulakos J,Marhin WH,Tokunaga J,Irish J,Gullane P,Penn LZ,Kamel-Reid S

    更新日期:2002-07-01 00:00:00

  • Protein Phosphatase 1 Regulatory Subunit SDS22 Inhibits Breast Cancer Cell Tumorigenesis by Functioning as a Negative Regulator of the AKT Signaling Pathway.

    abstract::Protein phosphatases play a crucial role in cell cycle progression, cell survival, cellular signaling, and genomic integrity. The protein phosphatase 1 (PP1) regulatory subunit SDS22 plays a significant role in cell cycle progression. A recent study showed that SDS22 plays a vital role in epithelial integrity and tumo...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2018.10.009

    authors: Paul D,Bargale AB,Rapole S,Shetty PK,Santra MK

    更新日期:2019-01-01 00:00:00

  • Neoplastic transformation induced by the gep oncogenes involves the scaffold protein JNK-interacting leucine zipper protein.

    abstract::The activated mutants of the α-subunits of G proteins G(12) and G(13) have been designated as the gep oncogenes owing to their ability to stimulate diverse oncogenic signaling pathways that lead to neoplastic transformation of fibroblast cell lines and tumorigenesis in nude mice models. Studies from our laboratory as ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.101622

    authors: Kashef K,Radhakrishnan R,Lee CM,Reddy EP,Dhanasekaran DN

    更新日期:2011-04-01 00:00:00

  • Noninvasive magnetic resonance spectroscopic pharmacodynamic markers of a novel histone deacetylase inhibitor, LAQ824, in human colon carcinoma cells and xenografts.

    abstract::The aim of this work was to use phosphorus magnetic resonance spectroscopy ((31)P MRS) to investigate the pharmacodynamic effects of LAQ824, a histone deacetylase (HDAC) inhibitor. Human HT29 colon carcinoma cells were examined by (31)P MRS after treatment with LAQ824 and another HDAC inhibitor, suberoylanilide hydrox...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.07834

    authors: Chung YL,Troy H,Kristeleit R,Aherne W,Jackson LE,Atadja P,Griffiths JR,Judson IR,Workman P,Leach MO,Beloueche-Babari M

    更新日期:2008-04-01 00:00:00

  • Cytokines and chemokines are expressed at different levels in small and large murine colon-26 tumors following intratumoral injections of CpG ODN.

    abstract::Direct tumor injections of (CpG ODN) into murine colon tumor 26 (CT-26) tumors can induce a potent antitumor response. Tumor size at the beginning of treatment determines the final therapeutic outcome, with smaller tumors responding favorably to CpG ODN therapy whereas large tumors do not. CpG ODN injections in small ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.04166

    authors: Sharma S,Karakousis CP,Takita H,Shin K,Brooks SP

    更新日期:2004-09-01 00:00:00

  • Molecular characterization of TMPRSS2-ERG gene fusion in the NCI-H660 prostate cancer cell line: a new perspective for an old model.

    abstract::Recent studies have established that a significant fraction of prostate cancers harbor a signature gene fusion between the 5' region of androgen-regulated TMPRSS2 and an ETS family transcription factor, most commonly ERG. Studies on the molecular mechanisms and functional consequences of this important chromosomal rea...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.07103

    authors: Mertz KD,Setlur SR,Dhanasekaran SM,Demichelis F,Perner S,Tomlins S,Tchinda J,Laxman B,Vessella RL,Beroukhim R,Lee C,Chinnaiyan AM,Rubin MA

    更新日期:2007-03-01 00:00:00

  • Antibody-dependent cell-mediated cytotoxicity effector-enhanced EphA2 agonist monoclonal antibody demonstrates potent activity against human tumors.

    abstract::EphA2 is a receptor tyrosine kinase that has been shown to be overexpressed in a variety of human tumor types. Previous studies demonstrated that agonist monoclonal antibodies targeting EphA2 induced the internalization and degradation of the receptor, thereby abolishing its oncogenic effects. In this study, the in vi...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.81578

    authors: Bruckheimer EM,Fazenbaker CA,Gallagher S,Mulgrew K,Fuhrmann S,Coffman KT,Walsh W,Ready S,Cook K,Damschroder M,Kinch M,Kiener PA,Woods R,Gao C,Dall'Acqua W,Wu H,Coats S

    更新日期:2009-06-01 00:00:00

  • Surface expression of precursor N-cadherin promotes tumor cell invasion.

    abstract::The expression of N-cadherin (NCAD) has been shown to correlate with increased tumor cell motility and metastasis. However, NCAD-mediated adhesion is a robust phenomenon and therefore seems to be inconsistent with the "release" from intercellular adhesion required for invasion. We show that in the most invasive melano...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.10954

    authors: Maret D,Gruzglin E,Sadr MS,Siu V,Shan W,Koch AW,Seidah NG,Del Maestro RF,Colman DR

    更新日期:2010-12-01 00:00:00

  • Clinical implications of promoter hypermethylation in RASSF1A and MGMT in retinoblastoma.

    abstract::We investigated the epigenetic silencing and genetic changes of the RAS-associated domain family 1A (RASSF1A) gene and the O6-methylguanine-DNA methyltransferase (MGMT) gene in retinoblastoma. We extracted DNA from microdissected tumor and normal retina tissues of the same patient in 68 retinoblastoma cases. Promoter ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.04565

    authors: Choy KW,Lee TC,Cheung KF,Fan DS,Lo KW,Beaverson KL,Abramson DH,Lam DS,Yu CB,Pang CP

    更新日期:2005-03-01 00:00:00

  • JAK kinase inhibition abrogates STAT3 activation and head and neck squamous cell carcinoma tumor growth.

    abstract::Aberrant activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) 3 has been implicated in cell proliferation and survival of many cancers including head and neck squamous cell carcinoma (HNSCC). AZD1480, an orally active pharmacologic inhibitor of JAK1/JAK2, has been tested in seve...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2015.01.003

    authors: Sen M,Pollock NI,Black J,DeGrave KA,Wheeler S,Freilino ML,Joyce S,Lui VW,Zeng Y,Chiosea SI,Grandis JR

    更新日期:2015-03-01 00:00:00

  • Bcl-2 and M-Myc coexpression increases IGF-IR and features of malignant growth in neuroblastoma cell lines.

    abstract::The bcl-2 and c-myc oncogenes cooperate to transform multiple cell types. In the pediatric malignancy NB(2), Bcl-2 is highly expressed. In tumors with a poor prognosis, N-Myc, a protein homologous to c-Myc, is overexpressed as a result of gene amplification. The present study was designed to determine whether Bcl-2 co...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900171

    authors: Jasty R,van Golen C,Lin HJ,Solomon G,Heidelberger K,Polverini P,Opipari A,Feldman E,Castle VP

    更新日期:2001-07-01 00:00:00

  • Valproic acid, an antiepileptic drug with histone deacetylase inhibitory activity, potentiates the cytotoxic effect of Apo2L/TRAIL on cultured thoracic cancer cells through mitochondria-dependent caspase activation.

    abstract::Inhibitors of histone deacetylases have been shown to enhance the sensitivity of cancer cells to tumor necrosis factor-related apoptosis-inducing ligand TRAIL-mediated cytotoxicity. Valproic acid (VA), a commonly used antiepileptic agent whose pharmacokinetics and toxicity profiles are well described, is a histone dea...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.05823

    authors: Ziauddin MF,Yeow WS,Maxhimer JB,Baras A,Chua A,Reddy RM,Tsai W,Cole GW Jr,Schrump DS,Nguyen DM

    更新日期:2006-06-01 00:00:00

  • Identification and characterization of CD44RC, a novel alternatively spliced soluble CD44 isoform that can potentiate the hyaluronan binding activity of cell surface CD44.

    abstract::Soluble CD44 proteins generated by proteolytic cleavage or aberrant intron retention have been shown to antagonize the ligand binding activity of the corresponding cell surface receptor, inducing apoptosis and inhibiting tumor growth. Interestingly, such findings appear to contradict recent studies demonstrating a cor...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900045

    authors: Chiu RK,Carpenito C,Dougherty ST,Hayes GM,Dougherty GJ

    更新日期:1999-11-01 00:00:00

  • Somatic copy number alterations are associated with EGFR amplification and shortened survival in patients with primary glioblastoma.

    abstract::Glioblastoma (GBM) is the most common malignant primary tumor of the central nervous system. With no effective therapy, the prognosis for patients is terrible poor. It is highly heterogeneous and EGFR amplification is its most frequent molecular alteration. In this light, we aimed to examine the genetic heterogeneity ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2019.09.001

    authors: Muñoz-Hidalgo L,San-Miguel T,Megías J,Monleón D,Navarro L,Roldán P,Cerdá-Nicolás M,López-Ginés C

    更新日期:2020-01-01 00:00:00

  • 15-lipoxygenase-1 expression upregulates and activates insulin-like growth factor-1 receptor in prostate cancer cells.

    abstract::We previously discovered that a fat-metabolizing enzyme, 15-lipoxygenase-1 (15-LO-1), is high in human prostate cancer (PCa) and correlates with disease progression. The biologic link between the aberrant 15-LO-1/linoleic acid (LA) metabolism and fat (which is a rich source of growth factors) in PCa is unknown. Theref...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/s1476-5586(04)80052-6

    authors: Kelavkar UP,Cohen C

    更新日期:2004-01-01 00:00:00

  • Characterization and Targeting of Platelet-Derived Growth Factor Receptor alpha (PDGFRA) in Inflammatory Breast Cancer (IBC).

    abstract:PURPOSE:Inflammatory breast cancer (IBC) is arguably the deadliest form of breast cancer due to its rapid onset and highly invasive nature. IBC carries 5- and 10-year disease-free survival rates of ~45% and <20%, respectively. Multiple studies demonstrate that in comparison with conventional breast cancer, IBC has a un...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2017.03.002

    authors: Joglekar-Javadekar M,Van Laere S,Bourne M,Moalwi M,Finetti P,Vermeulen PB,Birnbaum D,Dirix LY,Ueno N,Carter M,Rains J,Ramachandran A,Bertucci F,van Golen KL

    更新日期:2017-07-01 00:00:00

  • Twist modulates breast cancer stem cells by transcriptional regulation of CD24 expression.

    abstract::The cancer stem cell paradigm postulates that dysregulated tissue-specific stem cells or progenitor cells are precursors for cancer biogenesis. Consequently, identifying cancer stem cells is crucial to our understanding of cancer progression and for the development of novel therapeutic agents. In this study, we demons...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.91084

    authors: Vesuna F,Lisok A,Kimble B,Raman V

    更新日期:2009-12-01 00:00:00

  • Radiocurability is associated with interstitial fluid pressure in human tumor xenografts.

    abstract::Interstitial fluid pressure (IFP) has been shown to be an independent prognostic parameter for disease-free survival in cervical carcinoma patients treated with radiation therapy. However, the underlying mechanisms are not fully understood. The main aims of this study were to investigate whether tumor radiocurability ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.91152

    authors: Rofstad EK,Gaustad JV,Brurberg KG,Mathiesen B,Galappathi K,Simonsen TG

    更新日期:2009-11-01 00:00:00

  • Vascular differences detected by MRI for metastatic versus nonmetastatic breast and prostate cancer xenografts.

    abstract::Several studies have linked vascular density, identified in histologic sections, to "metastatic risk." Functional information of the vasculature, not readily available from histologic sections, can be obtained with contrast-enhanced MRI to exploit for therapy or metastasis prevention. Our aims were to determine if hum...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900129

    authors: Bhujwalla ZM,Artemov D,Natarajan K,Ackerstaff E,Solaiyappan M

    更新日期:2001-03-01 00:00:00

  • Elevated p21-activated kinase 2 activity results in anchorage-independent growth and resistance to anticancer drug-induced cell death.

    abstract::p21-activated kinase 2 (PAK-2) seems to be a regulatory switch between cell survival and cell death signaling. We have shown previously that activation of full-length PAK-2 by Rac or Cdc42 stimulates cell survival, whereas caspase activation of PAK-2 to the proapoptotic PAK-2p34 fragment is involved in the cell death ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.81446

    authors: Marlin JW,Eaton A,Montano GT,Chang YW,Jakobi R

    更新日期:2009-03-01 00:00:00

  • VEGFR3 inhibition chemosensitizes ovarian cancer stemlike cells through down-regulation of BRCA1 and BRCA2.

    abstract::In ovarian cancer, loss of BRCA gene expression in tumors is associated with improved response to chemotherapy and increased survival. A means to pharmacologically downregulate BRCA gene expression could improve the outcomes of patients with BRCA wild-type tumors. We report that vascular endothelial growth factor rece...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2014.04.003

    authors: Lim JJ,Yang K,Taylor-Harding B,Wiedemeyer WR,Buckanovich RJ

    更新日期:2014-04-01 00:00:00

  • Individual telomere lengths in chronic myeloid leukemia.

    abstract::Chronic myeloid leukemia (CML) is a neoplasia characterized by proliferation of a myeloid cell lineage and chromosome translocation t(9;22) (q34;q11.2). As in the case of most cancers, the average telomere length in CML cells is shorter than that in normal blood cells. However, there are currently no data available co...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.09836

    authors: Samassekou O,Ntwari A,Hébert J,Yan J

    更新日期:2009-11-01 00:00:00