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Search Results: 1 - 10 of 9584 matches for " Marc Cartellieri "
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Chimeric Antigen Receptor-Engineered T Cells for Immunotherapy of Cancer
Marc Cartellieri,Michael Bachmann,Anja Feldmann,Claudia Bippes,Slava Stamova,Rebekka Wehner,Achim Temme,Marc Schmitz
Journal of Biomedicine and Biotechnology , 2010, DOI: 10.1155/2010/956304
Abstract: CD4
Determination of the relative amounts of Gag and Pol proteins in foamy virus particles
Marc Cartellieri, Wolfram Rudolph, Ottmar Herchenr?der, Dirk Lindemann, Axel Rethwilm
Retrovirology , 2005, DOI: 10.1186/1742-4690-2-44
Abstract: One of the central features of Spumaretrovirinae, which distinguishes them from Orthoretrovirinae, is the expression of a Pol precursor protein independently of the Gag protein from a spliced mRNA [1-3]. This mechanism of Pol generation raises several interesting questions: (i) How is Pol expression regulated? (ii) How is the Pol protein incorporated into the virion? (iii) And how much Pol protein is actually present in infectious viruses? While question one has, to our knowledge, not been investigated yet, answers to question two are emerging [4,5]. Here we tried to address question three.Theoretical lines of argument favor the view that only a few molecules of Pol may be incorporated into a FV particle. The reverse transcriptase (RT) is the main enzymatic subunit of the Pol precursor [6]. This enzyme has been shown to be of much higher processivity than orthoretroviral RTs [7,8]. Therefore, it was argued that FVs probably encapsidate less of their highly active Pol protein compared to orthoretroviruses [7,8]. Following this line of argument, it is noteworthy that the FV protease (PR) is contained within the 85 kD Pol subunit, which also bears the RT/RNaseH [6]. However, in contrast to orthoretroviruses, the FV PR cleaves the cognate Gag protein only once prior to or during budding [6]. Therefore, FV may need less amounts of PR enzyme than orthoretroviruses.Furthermore, experiments aimed to elucidate the mechanism of Pol protein particle incorporation (the above raised question two) indicated that Pol interacts with specific sequences on the (pre-) genomic RNA and that RNA serves as a bridging molecule between Gag (capsid) and Pol [4,5]. Two distinct elements on the RNA have been identified, which probably facilitate this interaction [4]. This can be regarded as another argument in support of only trace amounts of encapsidated Pol protein.Here we wanted to investigate the approximate relative ratio of Pol to Gag molecules in infectious virions on a biochemical leve
Tumor Evasion from T Cell Surveillance
Katrin T pfer,Stefanie Kempe,Nadja Müller,Marc Schmitz,Michael Bachmann,Marc Cartellieri,Gabriele Schackert,Achim Temme
Journal of Biomedicine and Biotechnology , 2011, DOI: 10.1155/2011/918471
Abstract: An intact immune system is essential to prevent the development and progression of neoplastic cells in a process termed immune surveillance. During this process the innate and the adaptive immune systems closely cooperate and especially T cells play an important role to detect and eliminate tumor cells. Due to the mechanism of central tolerance the frequency of T cells displaying appropriate arranged tumor-peptide-specific-T-cell receptors is very low and their activation by professional antigen-presenting cells, such as dendritic cells, is frequently hampered by insufficient costimulation resulting in peripheral tolerance. In addition, inhibitory immune circuits can impair an efficient antitumoral response of reactive T cells. It also has been demonstrated that large tumor burden can promote a state of immunosuppression that in turn can facilitate neoplastic progression. Moreover, tumor cells, which mostly are genetically instable, can gain rescue mechanisms which further impair immune surveillance by T cells. Herein, we summarize the data on how tumor cells evade T-cell immune surveillance with the focus on solid tumors and describe approaches to improve anticancer capacity of T cells.
Characterization of a Novel Single-Chain Bispecific Antibody for Retargeting of T Cells to Tumor Cells via the TCR Co-Receptor CD8
Irene Michalk, Anja Feldmann, Stefanie Koristka, Claudia Arndt, Marc Cartellieri, Armin Ehninger, Gerhard Ehninger, Michael P. Bachmann
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0095517
Abstract: There is currently growing interest in retargeting of effector T cells to tumor cells via bispecific antibodies (bsAbs). Usually, bsAbs are directed on the one hand to the CD3 complex of T cells and on the other hand to a molecule expressed on the surface of the target cell. A bsAb-mediated cross-linkage via CD3 leads to an activation of CD8+ T cells and consequently to killing of the target cells. In parallel, CD4+ T cells including TH1, TH2, TH17 cells and even regulatory T cells (Tregs) will be activated as well. Cytokines produced by CD4+ T cells can contribute to severe side effects e. g. life-threatening cytokine storms and, thinking of the immunosupressive function of Tregs, can even be counterproductive. Therefore, we asked whether or not it is feasible to limit retargeting to CD8+ T cells e. g. via targeting of the co-receptor CD8 instead of CD3. In order to test for proof of concept, a novel bsAb with specificity for CD8 and a tumor-associated surface antigen was constructed. Interestingly, we found that pre-activated (but not freshly isolated) CD8+ T cells can be retargeted via CD8-engaging bsAbs leading to an efficient lysis of target cells.
Cancer Immunotherapy by Retargeting of Immune Effector Cells via Recombinant Bispecific Antibody Constructs
Slava Stamova,Stefanie Koristka,Juliane Keil,Claudia Arndt,Anja Feldmann,Irene Michalk,Holger Bartsch,Claudia C. Bippes,Marc Schmitz,Marc Cartellieri,Michael Bachmann
Antibodies , 2012, DOI: 10.3390/antib1020172
Abstract: Immunotherapy has emerged as an alternative strategy to treat malignancies in addition to conventional radio- and chemotherapy. There has been a plethora of evidence that the immune system is able to control tumor outgrowth and a number of strategies have been put forward to utilize this ability for immunotherapy. However, some of these strategies have not been very efficient and their success has been limited by tumor evasion mechanisms. A promising approach to engage effector cells of the immune system overcoming some of the escape mechanisms has been introduced more than two decades ago. This approach is based on bispecific antibodies. Here we summarize the evolution of bispecific antibodies, their improvement, remaining obstacles and some controversial reports.
A Novel Modular Antigen Delivery System for Immuno Targeting of Human 6-sulfo LacNAc-Positive Blood Dendritic Cells (SlanDCs)
Claudia C. Bippes,Anja Feldmann,Slava Stamova,Marc Cartellieri,Adrian Schwarzer,Rebekka Wehner,Marc Schmitz,E. Peter Rieber,Senming Zhao,Knut Sch?kel,Achim Temme,R. Hal Scofield,Biji T. Kurien,Holger Bartsch,Michael Bachmann
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0016315
Abstract: Previously, we identified a major myeloid-derived proinflammatory subpopulation of human blood dendritic cells which we termed slanDCs (e.g. Sch?kel et al. (2006) Immunity 24, 767–777). The slan epitope is an O-linked sugar modification (6-sulfo LacNAc, slan) of P-selectin glycoprotein ligand-1 (PSGL-1). As slanDCs can induce neoantigen-specific CD4+ T cells and tumor-reactive CD8+ cytotoxic T cells, they appear as promising targets for an in vivo delivery of antigens for vaccination. However, tools for delivery of antigens to slanDCs were not available until now. Moreover, it is unknown whether or not antigens delivered via the slan epitope can be taken up, properly processed and presented by slanDCs to T cells.
A Novel Ex Vivo Isolation and Expansion Procedure for Chimeric Antigen Receptor Engrafted Human T Cells
Marc Cartellieri, Stefanie Koristka, Claudia Arndt, Anja Feldmann, Slava Stamova, Malte von Bonin, Katrin T?pfer, Thomas Krüger, Mathias Geib, Irene Michalk, Achim Temme, Martin Bornh?user, Dirk Lindemann, Gerhard Ehninger, Michael P. Bachmann
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0093745
Abstract: Genetically engineered T lymphocytes are a promising option for cancer therapy. Prior to adoptive transfer they have to be expanded in vitro to reach therapeutically sufficient numbers. So far, no universal method exists for selective in vitro expansion of engineered T lymphocytes. In order to overcome this problem and for proof of concept we incorporated a novel unique peptide sequence of ten amino acids as epitope (E-Tag) into the binding domains of two novel chimeric antigen receptors (ECARs) directed against either prostate stem cell antigen (PSCA) for the treatment of prostate cancer (PCa) or CD33 for the treatment of acute myeloide leukemia (AML). The epitope tag then was utilized for expanding ECAR engrafted T cells by triggering the modified T cells via a monoclonal antibody directed against the E-Tag (Emab). Moreover, the E-Tag served as an efficient selection epitope for immunomagnetic isolation of modified T cells to high purity. ECAR engrafted T cells were fully functional and mediated profound anti-tumor effects in the respective models of PCa or AML both in vitro and in vivo. The method can be integrated straightforward into clinical protocols to improve therapeutic efficiency of tumor treatment with CAR modified T lymphocytes.
Editorial Article for the Journal of Microscopy Research  [PDF]
Marc Porti
Microscopy Research (MR) , 2013, DOI: 10.4236/mr.2013.12002
Abstract: Editorial; MR
Ionic Group Derivitized Nano Porous Carbon Electrodes for Capacitive Deionization  [PDF]
Marc Andelman
Journal of Materials Science and Chemical Engineering (MSCE) , 2014, DOI: 10.4236/msce.2014.23002
Abstract:

Capacitance for electrostatic adsorption forms primarily within a Debye length of the electrode surface. Capacitive carbon electrodes were derivatized with ionic groups by means of adsorbing a surfactant in order to test the theory that attached ionic groups would exclude co-ions and increase coulombic efficiency without the need for an added charge barrier membrane. It has been discovered that capacitive electrodes surface derivatized with ionic groups become polarized and intrinsically more coulombically efficient.

Soldner Had Found in 1802 the Deflection of the Light by the Sun as the General Relativity Shows  [PDF]
Marc Mignonat
Journal of Modern Physics (JMP) , 2018, DOI: 10.4236/jmp.2018.98095
Abstract: Systematically, it is written in the literature that only the general relativity (GR) allows finding the just value of the deflection of the light by the sun. Yet, we noted, by reading over the original text of SOLDNER of 1801: “Ueber die Ablenkung eines Lichtstrals von seiner geradlinigen Bewegung, durch die Attraktion eines Weltkörpers, the welchem er nahe vorbei geht” (that we think it is important to put in English in full in Appendix) that, contrary to what we read since about 100 years, he found the right value. Soldner had started from a Newtonian gravitational calculation and, with the value of 1801, find 1.64”. This calculation, with the actual values, allows finding the right value of 1.752”. There are reasons to explain the wrong calculations which we usually make. However, there is no epistemological reason for questioning the general relativity. Some observations are only explained by the GR. But the Newtonian calculations are much simpler. We can continue to say that the theory of Newton is incomplete but we cannot say it is false.
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