Abstract:
:Measles viruses (MV) are rapidly inactivated by anti-measles neutralizing antibodies, which has limited their clinical performance as oncolytic agents. Here, by substituting the H and F surface glycoproteins of MV with those from the homologous canine distemper virus (CDV) and engineering the CDV H attachment protein to target EGFR or CD38, we generated a fully retargeted MV capable of resisting neutralization by measles-immune human serum. The resultant recombinant MVs encoding retargeted CDV envelope glycoproteins had similar growth kinetics as the control MV, showed the expected engineered receptor specificities for cell entry, intercellular fusion, and target cell killing, and were blind to native CDV receptors. In contrast to the control MV, recombinant MVs incorporating CDV F and H glycoproteins retained full infectivity when exposed to high concentrations of pooled measles-immune human serum. Comparing viruses bearing MV or CDV glycoproteins in the SKOV3ip.1 model, only the virus bearing an EGFR-retargeted CDV envelope glycoprotein complex was capable of limiting tumor growth and extending the survival in measles immune mice. MV, "stealthed" and retargeted using engineered CDV surface glycoproteins, may be a promising platform to advance for systemic cancer therapy in measles immune patients.
journal_name
Mol Cancer Therjournal_title
Molecular cancer therapeuticsauthors
Bah ES,Nace RA,Peng KW,Muñoz-Alía MÁ,Russell SJdoi
10.1158/1535-7163.MCT-20-0134subject
Has Abstractpub_date
2020-10-01 00:00:00pages
2057-2067issue
10eissn
1535-7163issn
1538-8514pii
1535-7163.MCT-20-0134journal_volume
19pub_type
杂志文章abstract::Studies have shown the prognostic significance of disseminated tumor cells (DTC) in bone marrow of patients with colorectal cancer. However, the molecular characteristics of DTCs, including their miRNA expression profiles, remain mostly unknown. In this study, we analyzed the miRNA expression of DTCs in bone marrow. E...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-13-0571
更新日期:2014-04-01 00:00:00
abstract::Acquired resistance to cancer drugs is common, also for modern targeted drugs like the Bruton tyrosine kinase (BTK) inhibitor ibrutinib, a new drug approved for the treatment of the highly aggressive and relapsing mantle cell lymphoma (MCL). The tumor microenvironment often impacts negatively on drug response. Here, w...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-17-0784
更新日期:2018-05-01 00:00:00
abstract::Nasopharyngeal carcinoma (NPC) is a common cancer in Southern China and EBV is the most important pathogenesis. In this study, we explore the potential that a recombinant adeno-associated virus (rAAV) carrying a fusing gene containing heat shock protein as an adjuvant, EBV latent membrane proteins (LMP1 and LMP2) CTL ...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-08-1176
更新日期:2009-09-01 00:00:00
abstract::Epithelial ovarian cancer is characterized by a low recovery rate because the disease is typically diagnosed at an advanced stage, by which time most patients (80%) already exhibit disseminated neoplasia. The cytokine receptor CXCR4 has been implicated in the development of metastasis in various tumor types. Using a p...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-17-0643
更新日期:2018-02-01 00:00:00
abstract::A quaternary ammonium-based drug-linker has been developed to expand the scope of antibody-drug conjugate (ADC) payloads to include tertiary amines, a functional group commonly present in biologically active compounds. The linker strategy was exemplified with a β-glucuronidase-cleavable auristatin E construct. The dru...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-16-0038
更新日期:2016-05-01 00:00:00
abstract::Checkpoint kinase 1 (ChK1) is a serine/threonine kinase that functions as a central mediator of the intra-S and G2-M cell-cycle checkpoints. Following DNA damage or replication stress, ChK1-mediated phosphorylation of downstream effectors delays cell-cycle progression so that the damaged genome can be repaired. As a t...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-12-1218
更新日期:2013-10-01 00:00:00
abstract::The development of new drugs against cancer requires established cell lines. They are needed for in vitro studies to identify candidate drugs and in xenograft models to measure drug efficacy in vivo. Specific criteria need to be fulfilled by cell lines used in the evaluation of potential novel therapeutic agents. It i...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:
更新日期:2003-07-01 00:00:00
abstract::Peroxisome proliferator-activated receptor γ (PPARγ) is an important transcription factor that modulates lipid metabolism and inflammation. However, it remains unclear whether PPARγ is involved in modulation of estrogen (E2)-induced inflammation, thus affecting apoptosis of E2-deprived breast cancer cells, MCF-7:5C an...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-18-0088
更新日期:2018-12-01 00:00:00
abstract:OBJECTIVES:Emerging evidence implicates the SNAIL family of transcriptional repressors in cancer development; however, the role of SNAIL in colorectal cancer has not been established. To investigate the importance of SNAIL in colorectal carcinogenesis, we examined the phenotypic and cellular consequences of SNAIL down-...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:
更新日期:2004-09-01 00:00:00
abstract::B-Raf is an important mediator of cell proliferation and survival signals transduced via the Ras-Raf-MEK-ERK cascade. BRAF mutations have been detected in several tumors, including papillary thyroid carcinoma, but the precise role of B-Raf as a therapeutic target for thyroid carcinoma is still under investigation. We ...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-06-0449
更新日期:2007-03-01 00:00:00
abstract::The humanized anti-HER2 monoclonal antibody (mAb) trastuzumab (Herceptin; Genentech) effectively inhibits human epidermal growth factor receptor 2 (HER2)-positive breast tumors. However, many patients responding to treatment often develop resistance. Cross-talk between type I insulin-like growth factor receptor (IGF-I...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-13-0558
更新日期:2014-01-01 00:00:00
abstract::Breast cancer exhibits a propensity to metastasize to bone, resulting in debilitating skeletal complications associated with significant morbidity and poor prognosis. The cross-talk between metastatic cancer cells and bone is critical to the development and progression of bone metastases. We have shown the involvement...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-11-0277
更新日期:2012-01-01 00:00:00
abstract::Flex-Het drugs induce apoptosis in multiple types of cancer cells, with little effect on normal cells. This apoptosis occurs through the intrinsic mitochondrial pathway accompanied by generation of reactive oxygen species (ROS). The objective of this study was to determine if direct or indirect targeting of mitochondr...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-06-0279
更新日期:2007-06-01 00:00:00
abstract::Ligation of OX40 (CD134, TNFRSF4) on activated T cells by its natural ligand (OX40L, CD252, TNFSF4) enhances cellular survival, proliferation, and effector functions such as cytokine release and cellular cytotoxicity. We engineered a recombinant human OX40L IgG4P Fc fusion protein termed MEDI6383 that assembles into a...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-17-0200
更新日期:2018-05-01 00:00:00
abstract::We investigated integrin-linked kinase (ILK), a focal adhesion serine-threonine protein kinase, as a new molecular target for treating anaplastic thyroid cancer. ILK mediates cell growth and survival signals and is overexpressed in a number of cancers. Therefore, we hypothesized that inhibition of ILK leads to growth ...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-05-0078
更新日期:2005-08-01 00:00:00
abstract::The MET receptor tyrosine kinase, the receptor for hepatocyte growth factor (HGF), has been implicated in cancer growth, invasion, migration, angiogenesis, and metastasis in a broad variety of human cancers, including human hepatocellular carcinoma (HCC). Recently, MET was suggested to be a potential target for the pe...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-14-0780
更新日期:2015-11-01 00:00:00
abstract::Eribulin (E7389), a synthetic analogue of halichondrin B in phase III clinical trials for breast cancer, binds to tubulin and microtubules. At low concentrations, it suppresses the growth phase of microtubule dynamic instability in interphase cells, arrests mitosis, and induces apoptosis, suggesting that suppression o...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-08-0095
更新日期:2008-07-01 00:00:00
abstract::Cell cycle regulators, such as the CDC25 phosphatases, are potential targets for the development of new anticancer drugs. Here we report the identification and the characterization of BN82685, a quinone-based CDC25 inhibitor that is active in vitro and in vivo. BN82685 inhibits recombinant CDC25A, B, and C phosphatase...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-05-0168
更新日期:2005-09-01 00:00:00
abstract::The expression of cyclooxygenase (COX)-2 is increased in human cancers including cholangiocarcinoma. This study was designed to evaluate the effect and mechanisms of the selective COX-2 inhibitor celecoxib in the growth control of human cholangiocarcinoma cells. Immunohistochemical analysis using human cholangiocarcin...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:
更新日期:2004-03-01 00:00:00
abstract::Tolfenamic acid (TA) is a nonsteroidal anti-inflammatory drug that inhibits pancreatic cancer cell and tumor growth through decreasing expression of specificity protein (Sp) transcription factors. TA also inhibits growth of erbB2-overexpressing BT474 and SKBR3 breast cancer cells; however, in contrast to pancreatic ca...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-08-1097
更新日期:2009-05-01 00:00:00
abstract::One hallmark of cancer cells is their adaptation to rely upon an altered metabolic scheme that includes changes in the glycolytic pathway, known as the Warburg effect, and elevated glutamine metabolism. Glutaminase, a mitochondrial enzyme, plays a key role in the metabolism of glutamine in cancer cells, and its inhibi...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-11-0942
更新日期:2012-06-01 00:00:00
abstract::Chronic myelogenous leukemia is characterized by the presence of the chimeric BCR-ABL gene, which is expressed as the constitutively active Bcr-Abl kinase. Although kinase activity is directly responsible for the clinical phenotype, current diagnostic and prognostic methods focus on a genetic classification system in ...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-10-0157
更新日期:2010-05-01 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) is one of the most chemotherapy- and radiotherapy-resistant tumors. The c-Met and Hedgehog (Hh) pathways have been shown previously by our group to be key regulatory pathways in the primary tumor growth and metastases formation. Targeting both the HGF/c-Met and Hh pathways has s...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-16-0452
更新日期:2017-11-01 00:00:00
abstract::Phortress is a novel, potent, and selective experimental antitumor agent. Its mechanism of action involves induction of CYP1A1-catalyzed biotransformation of 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203) to generate electrophilic species, which covalently bind to DNA, exacting lethal damage to sensitive tu...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:
更新日期:2004-12-01 00:00:00
abstract::Upregulation of HER2 is a hallmark of 20% to 30% of invasive breast cancers, rendering this receptor an attractive target for cancer therapy. Although HER2-targeting agents have provided substantial clinical benefit as cancer therapeutics, there is a need for the development of new agents aiming at circumventing anti-...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-14-0046-T
更新日期:2014-08-01 00:00:00
abstract::We have developed a near-infrared (NIR) probe that targets cells overexpressing the EGF receptor (EGFR) for imaging glioblastoma brain tumors in live subjects. A peptide specific for the EGFR was modified with various lengths of monodiscrete polyethylene glycol (PEG) units and a NIR Cy5.5 fluorescence dye. The lead co...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-12-0211
更新日期:2012-10-01 00:00:00
abstract::The NF-κB transcription factor functions as a crucial regulator of cell survival and chemoresistance in pancreatic cancer. Recent studies suggest that tocotrienols, which are the unsaturated forms of vitamin E, are a promising class of anticancer compounds that inhibit the growth and survival of many cancer cells, inc...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-11-0424
更新日期:2011-12-01 00:00:00
abstract::DNA cytosine methylation plays a considerable role in normal development, gene regulation, and carcinogenesis. Hypermethylation of the promoters of some tumor suppressor genes and the associated silencing of these genes often occur in certain cancer types. The reversal of this process by DNA methylation inhibitors is ...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-05-0172
更新日期:2005-10-01 00:00:00
abstract::Targeting death receptor-mediated apoptosis has emerged as an effective strategy for cancer therapy. However, certain types of cancer cells are intrinsically resistant to death receptor-mediated apoptosis. In an effort to identify agents that can sensitize cancer cells to death receptor-induced apoptosis, we have iden...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-07-2409
更新日期:2008-07-01 00:00:00
abstract::RECQL1, a key member of the RecQ family of DNA helicases, is required for DNA replication and DNA repair. Two recent studies have shown that germline RECQL1 mutations are associated with increased breast cancer susceptibility. Whether altered RECQL1 expression has clinicopathologic significance in sporadic breast canc...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-16-0290
更新日期:2017-01-01 00:00:00