Cancer biology & therapy (Canc Biol Ther)

Publisher: Taylor & Francis

Journal description

Cancer, the second leading cause of death, is a heterogenous group of over 100 diseases. Cancer is characterized by disordered and deregulated cellular and stromal proliferation accompanied by reduced cell death with the ability to survive under stresses of nutrient and growth factor deprivation, hypoxia, and loss of cell-to-cell contacts. At the molecular level, cancer is a genetic disease that develops due to the accumulation of mutations over time in somatic cells. The phenotype includes genomic instability and chromosomal aneuploidy that allows for acceleration of genetic change. Malignant transformation and tumor progression of any cell requires immortalization, loss of checkpoint control, deregulation of growth, and survival. A tremendous amount has been learned about the numerous cellular and molecular genetic changes and the host-tumor interactions that accompany tumor development and progression. It is the goal of the field of Molecular Oncology to use this knowledge to understand cancer pathogenesis and drug action, as well as to develop more effective diagnostic and therapeutic strategies for cancer. This includes preventative strategies as well as approaches to treat metastases. With the availability of the human genome sequence and genomic and proteomic approaches, a wealth of tools and resources are generating even more information. The challenge will be to make biological sense out of the information, to develop appropriate models and hypotheses and to translate information for the clinicians and the benefit of their patients. Cancer Biology & Therapy aims to publish original research on the molecular basis of cancer, including articles with translational relevance to diagnosis or therapy. We will include timely reviews covering the broad scope of the journal. The journal will also publish op-ed pieces and meeting reports of interest. The goal is to foster communication and rapid exchange of information through timely publication of important results using traditional as well as electronic formats. The journal and the outstanding Editorial Board will strive to maintain the highest standards for excellence in all activities to generate a valuable resource.

Current impact factor: 3.63

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 Impact Factor 3.63
2012 Impact Factor 3.287
2011 Impact Factor 2.636
2010 Impact Factor 2.907
2009 Impact Factor 2.711
2008 Impact Factor 2.761
2007 Impact Factor 2.873
2006 Impact Factor 2.818
2005 Impact Factor 2.981
2004 Impact Factor 3.279
2003 Impact Factor 3.024

Impact factor over time

Impact factor
Year

Additional details

5-year impact 3.33
Cited half-life 4.70
Immediacy index 0.39
Eigenfactor 0.02
Article influence 1.00
Website Cancer Biology and Therapy website
Other titles Cancer biology & therapy (Online), Cancer biology & therapy, Cancer biology and therapy
ISSN 1555-8576
OCLC 60037853
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Taylor & Francis

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    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
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    • On author's personal website or departmental website immediately
    • On institutional repository or subject-based repository after either 12 months embargo
    • Publisher's version/PDF cannot be used
    • On a non-profit server
    • Published source must be acknowledged
    • Must link to publisher version
    • Set statements to accompany deposits (see policy)
    • The publisher will deposit in on behalf of authors to a designated institutional repository including PubMed Central, where a deposit agreement exists with the repository
    • STM: Science, Technology and Medicine
    • Publisher last contacted on 25/03/2014
    • This policy is an exception to the default policies of 'Taylor & Francis'
  • Classification
    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Quantification of Circulating Tumor Cells (CTCs) as a prognostic marker in metastatic colorectal cancer (mCRC) has already been validated and approved for routine use. However, more than quantification, qualification or characterization of CTCs is gaining importance, since the genetic characterization of CTCs may reflect, in a real time fashion, genetic profile of the disease. To characterize KRAS mutations (codon 12 and 13) in CTCs from patients with mCRC and to compare with matched primary tumor. Additionally, correlate these mutations with clinical and pathological features of patients. Blood samples were collected from 26 patients with mCRC from the AC Camargo Cancer Center. CTCs were isolated by ISET technology (Isolation by Size of Epithelial Tumors; Rarecells Diagnostics, France) and mutations analyzes were performed by pyrosequencing (QIAGEN). KRAS mutation was detected in 7 of the 21 cases (33%) of samples from CTCs. In matched primary tumors, 9 of the 24 cases (37.5%) were found KRAS mutated. We observed that 5 of the 9 samples with KRAS mutation in their primary tumor had also KRAS mutation in CTCs, meaning a concordance of 71% of matched cases (P=0.017). KRAS mutation neither on primary tumor nor in CTCs was associated with clinical-pathological parameters analyzed. Faced with a polyclonal disease like colorectal cancer, which is often treated with alternating and successive lines of chemotherapy, real time genetic characterization of CTCs, in a fast and feasible fashion, can provide important information to clinical management of metastatic patients. Although our cohort was limited, it was possible to show a high grade of concordance between primary tumor and CTCs, which suggests that CTCs can be used as surrogate of primary tumors in clinical practice, when the knowledge of mutation profile is necessary and the primary tumor is not available.
    Cancer biology & therapy 08/2015; DOI:10.1080/15384047.2015.1070991
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    ABSTRACT: Following a genotoxic stress, the tumor suppressor p53 translocates to mitochondria to take part in direct induction of apoptosis, via interaction with BCL-2 family members such as BAK and BAX. We determined the kinetics of the mitochondrial translocation of p53 in HCT-116 and PA-1 cells exposed to different genotoxic stresses (doxorubicin, camptothecin, UVB). This analysis revealed an early escalation in the amount of mitochondrial p53, followed by a peak amount and a decrease of mitochondrial p53 at later time points. We show that the serine 20 phosphorylated form of p53 is present at the mitochondria and that the decrease of p53 mitochondrial level during late apoptosis correlates with a decrease of Ser-20 phosphorylation. Moreover, the S20A p53 mutant translocates well to mitochondria after a genotoxic stress but its mitochondrial localization is very low during late apoptosis when compared to wt p53. The S20A mutant also appears to be compromised for interaction with BAK. We propose here that the level of serine 20 phosphorylation is influential on p53 mitochondrial localization during late apoptosis. Additionally, we report the presence of a new ≃45 kDa caspase-cleaved fragment of p53 in the cytosolic and mitochondrial fractions of apoptotic cells.
    Cancer biology & therapy 08/2015; DOI:10.1080/15384047.2015.1070978
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    ABSTRACT: Sphingolipid metabolism has been identified as a potential therapeutic target in cancer. Sphingosine-1-phosphate (S1P) is a potent bioactive sphingolipid metabolite produced by sphingosine kinases-1 and -2 (SPHK1 and SPHK2). Elevated SPHK1 has been found in numerous cancer types and been shown to contribute to survival, chemotherapeutic resistance and malignancy. However, its role in large granular Natural Killer (NK)-lymphocyte (LGL) leukemia has not been investigated. Here, we examine SPHK1 as a therapeutic target in LGL leukemia. We found that SPHK1 is overexpressed in peripheral blood mononuclear cells (PBMCs) from LGL leukemia patients which results in elevated S1P in the sera. The use of SPHK1 inhibitors, SKI-II or SKI-178, decreased leukemic NK cell viability and induced caspase-dependent apoptosis. SKI-II and SKI-178 restored the sphingolipid balance by increasing ceramide and decreasing S1P in leukemic NKL cells. SKI-II and SKI-178 also induced apoptosis in primary NK-LGLs from leukemia patients. Mechanistic studies in NK-LGL cell lines demonstrated that SKI-178 and SKI-II induced cell cycle arrest at G2M. We found that SKI-178 induced phosphorylation of Bcl-2 at Ser70, and that this was dependent on CDK1. We further show that SPHK1 inhibition with SKI-178 leads to decreased JAK-STAT signaling. Our data demonstrate that SPHK1 represents a novel therapeutic target for the treatment of NK-LGL leukemia.
    Cancer biology & therapy 08/2015; DOI:10.1080/15384047.2015.1078949
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    ABSTRACT: The Zinc finger X-chromosomal protein (ZFX), a novel member of the Krueppel C2H2-type zinc finger protein family, has been implicated in multiple human cancers. However, the clinical significance of ZFX expression in gallbladder cancer (GBC) remains largely unknown. In this study, we focused on the clinical significance, biological function and mechanism of ZFX in GBC, and found that ZFX protein overexpression was frequently detected in GBC tissues. The expression of ZFX was significantly correlated with histological grade, perineural invasion, and margin status and lead to a significantly poorer prognosis in GBC patients(P <0.001). Furthermore, knockdown of ZFX result in significant inhibition of proliferation, migration, invasion and cause cell cycle arrest in GBC-SD cells, while over-expression of ZFX in NOZ shows the opposite results. Activation of PI3K/AKT pathway maybe the potential mechanism behind these effects. In conclusion, ZFX may serve as a oncogene and could be used as a potential prognostic marker and genetic treatment target for GBC patients.
    Cancer biology & therapy 07/2015; DOI:10.1080/15384047.2015.1070994
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    ABSTRACT: A greater understanding of the molecular basis of breast cancer metastasis will lead to identification of novel therapeutic targets and better treatments. Rap1B is a small GTPase that suppresses the metastasis of breast cancer cells by increasing cell-cell adhesion. In breast cancer, a decrease in Rap1B prenylation and subsequent loss of Rap1B at the plasma membrane decreases cell-cell adhesion and increases cell scattering, which promotes the metastatic phenotype. Protein kinase A (PKA) was recently found to phosphorylate Rap1B and inhibit its prenylation. PKA is activated by G protein-coupled receptors (GPCR) that stimulate Gαs. In this study, we investigated whether the general Gαs activator, cholera toxin, and agonists of the β-adrenergic receptor (βAR), which is a Gαs-coupled GPCR, promote Rap1B phosphorylation and inhibit its prenylation. We show here that cholera toxin and βAR activation phosphorylate Rap1B and inhibit its prenylation and membrane localization, reducing cell-cell adhesion and promoting cell scattering. Furthermore, we report that breast cancer cell migration is decreased by the FDA-approved β-blocker, propranolol. Pharmacological targeting of GPCRs, especially those such as the βAR that are regulated by FDA-approved drugs, to increase cell adhesion and decrease cell scattering could provide a promising therapeutic approach to reduce breast cancer metastasis.
    Cancer biology & therapy 07/2015; DOI:10.1080/15384047.2015.1070988
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    ABSTRACT: We previously established that hepatocyte cell adhesion molecule (hepaCAM), a typical structure of immunoglobulin (Ig)-like adhesion molecules, inhibited the proliferation and the progression of cultured human bladder cancer cells. As increasing evidence reveals that aberrant activation of canonical Wnt pathway is involved in the pathogenesis of bladder cancer, and β-catenin serves as a pivotal molecule of Wnt pathway. Then, we explored whether the anti-proliferation effect of hepaCAM was associated with Wnt/β-catenin pathway in human bladder cancer cells. The negative correlation between hepaCAM and β-catenin in transitional cell carcinoma of bladder (TCCB) was found. Follow by, studied the effect of hepaCAM on the key elements of Wnt pathway. Here, Our researches showed that hepaCAM played a central role in modulating the Wnt/β-catenin signaling pathway by interfering nuclear protein levels of β-catenin, leading to down-regulate transcriptional activity of LEF/TCF and its target genes c-Myc and cyclinD1. Mechanistically, we demonstrated that hepaCAM-activated GSK3β led to elevate the phosphorylation of β-catenin, contributing to the aberrant translocation of β-catenin. In addition, Anti-proliferation and associated molecular mechanisms of hepaCAM were demonstrated by using vivo experiment. In conclusion, our reports uncover that expression of hepaCAM suppresses the proliferation of bladder cancer cells through a Wnt/β-catenin-dependent signaling pathway in vitro and in vivo.
    Cancer biology & therapy 07/2015; DOI:10.1080/15384047.2015.1071732
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    ABSTRACT: In a previous study we reported the role of potent bisindole-PBD conjugate as an inclusion in the arsenal of breast cancer therapeutics. In breast cancer cell proliferation, PI3K/AKT/mTOR pathway plays a crucial role by prosurvival mechanism that inhibits programmed cell death. Here, two breast cancer cells lines, MCF-7 and MDA-MB-231 were treated with Vorinostat (suberoylanilide hydroxamic acid / SAHA) and bisindole-PBD (5b). We have investigated the effect on PI3K/AKT/mTOR pathway and SIRT expression including epigenetic regulation. There was consistent decrease in the level of PI3K, AKT, mTOR proteins upon treatment of 5b in both MCF-7 and MDA-MB-231 cell lines compared to untreated controls. Treatment with caspase inhibitor (Q-VD-OPH) confirmed that the effect of 5b on PI3K signaling was ahead of apoptosis. Real time PCR and western blot analysis showed profound reduction in the mRNA and protein levels of SIRT1 and SIRT2. Molecular docking studies also supported the interaction of 5b with various amino acids of SIRT2 proteins. Treatment with 5b caused epigenetic changes that include increase of acetylated forms of p53, increase of histone acetylation at p21 promoter as well as decrease in methylation state of p21 gene. Compound 5b thus acts as SIRT inhibitor and cause p53 activation via inhibition of growth factor signaling and activation of p53 dependent apoptotic signaling. This present study focuses bisindole-PBD on epigenetic alteration putting 5b as a promising therapeutic tool in the realm of breast cancer research.
    Cancer biology & therapy 07/2015; DOI:10.1080/15384047.2015.1071731
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    ABSTRACT: CD123 bacame a therapeutic target for acute myelocytic leukemia(AML) because of its overexpression only on AML stem cells.It is αsubunit of interleukin-3 (multi-CSF, IL3) receptor. Lidamycin(LDM) is a novle antibiotic composed of an apoprotein(LDP) and a chromophore(AE). We cloned, expressed and isolated IL3LDP fusion protein first then assembled with AE in vitro. We found that131/132 amino acids of IL3 were the key factors for IL3 fusion protein stability and I131L/F132L mutation effectively improved the IL3 fusion protein stability.The toxicity of IL3LDM to CD123+ tumor cells was 2-10 times compared to LDM alone and 10000 times compared to ADR. Meanwhile, IL3LDM impaired the colony-forming ability of CD123+ stem-like cells but not to CD123 negtive normal cord blood cells. Three drug delivery methods in vivo were adopted: prophylactic treatment and single/multiple-dosing administration. The tumor-free survival extended to 120 days and cancer cell invasion significantly decreased after IL3LDM continuous multiple treated. Moreover, IL3LDM had been shown to modulate apoptosis by arrested cell cycle in G2/M phase. Therefore, IL3LDM is expected to be a new drug for leukemia target therapy.
    Cancer biology & therapy 07/2015; DOI:10.1080/15384047.2015.1071733
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    ABSTRACT: Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR; ErbB1) - either exon 19 deletions or exon 21 point mutations - are associated with hypersensitivity to EGFR tyrosine kinase inhibitors (TKIs). EGFR mutations are more frequently found in females, non-smokers, Asians, and patients with adenocarcinoma. We report the case of a 51-year-old Caucasian woman with metastatic NSCLC harboring an EGFR exon 19 deletion although she was a smoker and had a poorly differentiated large cell carcinoma. Following a partial response on four months of chemotherapy, the patient progressed and was treated with the reversible EGFR TKI erlotinib for 3 years. The patient then developed resistance to erlotinib and went on to receive the irreversible ErbB Family Blocker afatinib for 1 year, attaining a partial response at four months. The impressive survival time attained by our patient highlights the clinical benefit of targeting one or more members of the ErbB Family in patients with disseminated NSCLC and EGFR activating mutations.
    Cancer biology & therapy 07/2015; DOI:10.1080/15384047.2015.1070993
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    ABSTRACT: Aquaporin 1 (AQP1), a member of water channel proteins, functions as a water-selective transporting protein in cell membranes. In recent years, AQP1 has been found to be overexpressed in various tumors. However, the molecular mechanism underlying the biological function of AQP1 in osteosarcoma is still unclear. This study was aimed at elucidating the roles of AQP1 in regulating the biological behavior of osteosarcoma cells. In this study, we found that AQP1 mRNA was elevated in osteosarcoma tissue. High level of AQP1 was associated with poor prognosis in osteosarcoma. Then, we found that knockdown of AQP1 in osteosarcoma cells, U2OS or MG63 cells inhibited cell proliferation and significantly increased cells population in G1 phase. Additionally, suppressing AQP1 expression in osteosarcoma cells dramatically induced cell apoptosis. We also found that down-regulation of AQP1 significantly inhibited cell adhesion and invasion. More importantly, AQP1 knockdown inhibited tumor growth in vivo and prolonged the survival time of nude mice. Gene set enrichment analysis (GSEA) showed that transforming growth factor-β (TGF-β) signaling pathway and focal adhesion genes was correlatively with AQP1 expression. In addition, real time PCR and western blot analysis revealed that expression of TGF-β1/TGF-β2, RhoA and laminin beta 2 (LAMB2) was remarkably impaired by AQP1 silencing. In conclusion, AQP1 may be a useful diagnosis and prognosis marker for osteosarcoma. AQP1 knockdown can effectively inhibit cell proliferation, adhesion, invasion and tumorigenesis by targeting TGF-β signaling pathway and focal adhesion genes, which may serve a promising therapeutic strategy for osteosarcoma.
    Cancer biology & therapy 07/2015; DOI:10.1080/15384047.2015.1070983
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    ABSTRACT: Neuroblastoma is one of the most common solid tumors in childhood and usually accompanied with poor prognosis and rapid tumor progression when diagnosed with amplification of the proto-oncogene N-Myc. The amplification of N-Myc has major influence on the maintenance of aerobic glycolysis, also known as the Warburg effect. This specific switch in the conversion of pyruvate to lactate instead of the conversion of pyruvate to acetyl-coenzyme A even in the presence of oxygen has important benefits for the tumor, e.g. increased production of enzymes and enzyme substrates that are involved in tumor progression, angiogenesis and inhibition of apoptosis. The antiprotozoal drug nifurtimox, which is generally used for the treatment of infections with the parasitic protozoan Trypanosoma cruzi, has been reported to have cytotoxic properties in the therapy of neuroblastoma. However, its action of mechanism has not been described in detail yet. The presented in vitro study on the neuroblastoma cell lines LA-N-1, IMR-32, LS and SK-N-SH shows an increased production of oxidative stress, a reduced lactate dehydrogenase (LDH) enzyme activity and reduced lactate production after nifurtimox treatment. Furthermore, nifurtimox leads to reduced mRNA and protein levels of the proto-oncogene protein N-Myc. Thus, the current work gives new insights into the effect of nifurtimox on tumor metabolism revealing a shifted glucose metabolism from production of lactate to oxidative phosphorylation and a reduced expression of the major molecular prognostic factor in neuroblastoma N-Myc, presenting nifurtimox as a possible adjuvant therapeutic agent against (high risk) neuroblastoma. Download link: http://www.tandfonline.com/eprint/QebCYwkWWsPNDNs5P3sW/full
    Cancer biology & therapy 07/2015; DOI:10.1080/15384047.2015.1070987
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    ABSTRACT: Pixantrone is a novel aza-anthracenedione active against aggressive lymphoma and is being evaluated for use against various hematologic and solid tumors. The drug is an analogue of mitoxantrone, but displays less cardiotoxicity than mitoxantrone or the more commonly used doxorubicin. Although pixantrone is purported to inhibit topoisomerase II activity and intercalate with DNA, exact mechanisms of how it induces cell death remain obscure. Here we evaluated the effect of pixantrone on a panel of solid tumor cell lines to understand its mechanism of cell killing. Initial experiments with pixantrone showed an apparent discrepancy between its anti-proliferative effects in MTS assays (short-term) compared with clonogenic assays (long-term). Using live cell videomicroscopy to track the fates of cells, we found that cells treated with pixantrone underwent multiple rounds of aberrant cell division before eventually dying after approximately 5 days post-treatment. Cells underwent abnormal mitosis in which chromosome segregation was impaired, generating chromatin bridges between cells or within cells containing micronuclei. While pixantrone-treated cells did not display γH2AX foci, a marker of DNA damage, in the main nuclei, such foci were often detected in the micronuclei. Using DNA content analysis, we found that pixantrone concentrations that induced cell death in a clonogenic assay did not impede cell cycle progression, further supporting the lack of canonical DNA damage signaling. These findings suggest pixantrone induces a latent type of DNA damage that impairs the fidelity of mitosis, without triggering DNA damage response or mitotic checkpoint activation, but is lethal after successive rounds of aberrant division.
    Cancer biology & therapy 07/2015; DOI:10.1080/15384047.2015.1070979
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    ABSTRACT: Many genes controlling cell proliferation and survival (those most important to cancer biology) are now known to be regulated specifically at the translational (RNA to protein) level. The internal ribosome entry site (IRES) provides a mechanism by which the translational efficiency of an individual or group of mRNAs can be regulated independently of the global controls on general protein synthesis. IRES-mediated translation has been implicated as a significant contributor to the malignant phenotype and chemoresistance, however there has been no effective means by which to interfere with this specialized mode of protein synthesis. A cell-based empirical high-throughput screen was performed in attempt to identify compounds capable of selectively inhibiting translation mediated through the IGF1R IRES. Results obtained using the bicistronic reporter system demonstrate selective inhibition of second cistron translation (IRES-dependent). The lead compound and its structural analogs completely block de novo IGF1R protein synthesis in genetically-unmodified cells, confirming activity against the endogenous IRES. Spectrum of activity extends beyond IGF1R to include the c-myc IRES. The small molecule IRES inhibitor differentially modulates synthesis of the oncogenic (p64) and growth-inhibitory (p67) isoforms of Myc, suggesting that the IRES controls not only translational efficiency, but also choice of initiation codon. Sustained IRES inhibition has profound, detrimental effects on human tumor cells, inducing massive (>99%) cell death and complete loss of clonogenic survival in models of triple-negative breast cancer. The results begin to reveal new insights into the inherent complexity of gene-specific translational regulation, and the importance of IRES-mediated translation to tumor cell biology.
    Cancer biology & therapy 07/2015; DOI:10.1080/15384047.2015.1071729
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    ABSTRACT: Multidrug resistance and tumor migration and invasion are the major obstacles to effective breast cancer chemotherapy, but the underlying molecular mechanisms remain unclear. This study investigated the potential of transgelin 2 and salvianolic acid A to modulate the resistance and the migration and invasion abilities of paclitaxel-resistant human breast cancer cells (MCF-7/PTX). MCF-7/PTX cells were found to exhibit not only a high degree of resistance to paclitaxel, but also strong migration and invasion abilities. Small interfering RNA-mediated knockdown of TAGLN2 sensitized the MCF-7/PTX cells to paclitaxel, and inhibited their migration and invasion abilities. In addition, we also observed that combined salvianolic acid A and paclitaxel treatment could reverse paclitaxel resistance, markedly inhibit tumor migration and invasion, and suppress the expression of transgelin 2 in MCF-7/PTX cells. These findings indicate that salvianolic acid A can reverse the paclitaxel resistance and inhibit the migration and invasion abilities of human breast cancer cells by down-regulating the expression of transgelin 2, and hence could be useful in breast cancer treatments.
    Cancer biology & therapy 07/2015; DOI:10.1080/15384047.2015.1070990
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    ABSTRACT: Adoptive T-cell therapy of cancer often fails due to the tumour cells' immune escape mechanisms, like antigen loss or down-regulation. To anticipate immune escape by loss of a single antigen, it would be advantageous to equip T cells with multiple specificities. To study the possible interference of two T-cell receptors (TCRs) in one cell, and to examine how to counteract competing effects, we generated TETARs, CD8(+) T cells expressing two additional T-cell receptors by simultaneous transient transfection with two TCRs using RNA electroporation. The TETARs were equipped with one TCR specific for the common melanoma antigen gp100 and one TCR recognising a patient-specific, individual mutation of CCT6A (chaperonin containing TCP1, subunit 6A) termed "CCT6A(m) TCR". These CD8(+) T cells proved functional in cytokine secretion and lytic activity upon stimulation with each of their cognate antigens, although some reciprocal inhibition was observed. Murinisation of the CCT6A(m) TCR increased and prolonged its expression and increased the lytic capacity of the dual-specific T cells. Taken together, we generated functional, dual-specific CD8(+) T cells directed against a common melanoma-antigen and an individually mutated antigen for the use in personalised adoptive T-cell therapy of melanoma. The intended therapy would involve repetitive injections of the RNA-transfected cells to overcome the transiency of TCR expression. In case of autoimmunity-related side effects, a cessation of treatment would result in a disappearance of the introduced receptors, which increases the safety of this approach.
    Cancer biology & therapy 07/2015; DOI:10.1080/15384047.2015.1070981
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    ABSTRACT: To develop new diagnostic and therapeutic tools to specifically target pancreatic tumors, it is necessary to identify cell-surface proteins that may serve as potential tumor-specific targets. In this study we used an azido-labeled bioorthogonal chemical reporter to metabolically label N-linked glycoproteins on the surface of pancreatic cancer cell lines to identify potential targets that may be exploited for detection and/or treatment of pancreatic cancer. Labeled glycoproteins were tagged with biotin using click chemistry, purified by streptavidin-coupled magnetic beads, separated by gel electrophoresis, and identified by liquid chromatography-tandem mass spectrometry (MS). MS/MS analysis of peptides from three cell lines revealed 954 unique proteins enriched in the azido sugar samples relative to control sugar samples. A comparison of the proteins identified in each sample indicated 20% of these proteins were present in two cell lines (193 of 954) and 17 of the proteins were found in all three cell lines. Five of the 17 proteins identified in all three cell lines have not been previously reported to be expressed in pancreatic cancer; thus indicating that novel cell-surface proteins can be revealed through glycoprotein profiling. Western analysis of one of these glycoproteins, ecto-5'-nucleotidase (NT5E), revealed it is expressed in eight out of eight pancreatic cancer cell lines examined. Further, immunohistochemical analysis of human pancreatic tissues indicates NT5E is significantly overexpressed in pancreatic tumors compared to normal pancreas. Thus, we have demonstrated that metabolic labeling with bioorthogonal chemical reporters can be used to selectively enrich and identify novel cell-surface glycoproteins expressed in pancreatic ductal adenocarcinomas.
    Cancer biology & therapy 07/2015; DOI:10.1080/15384047.2015.1071740