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  1. Article ; Online: Novel insights into the HLA class I immunopeptidome and T-cell immunosurveillance

    Cornelis J. M. Melief / Jan H. Kessler

    Genome Medicine, Vol 9, Iss 1, Pp 1-

    2017  Volume 3

    Abstract: Editorial summary Advances in mass spectrometry have allowed the high-throughput quantitative identification of human leukocyte antigen (HLA) class I ligands, and recent studies have reported on the breadth and diversity of the HLA class I ... ...

    Abstract Editorial summary Advances in mass spectrometry have allowed the high-throughput quantitative identification of human leukocyte antigen (HLA) class I ligands, and recent studies have reported on the breadth and diversity of the HLA class I immunopeptidome. These findings have far-reaching implications for immunosurveillance by T cells and translational value for immunotherapy.
    Keywords Medicine ; R ; Genetics ; QH426-470
    Language English
    Publishing date 2017-05-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article: Effectiveness of slow-release systems in CD40 agonistic antibody immunotherapy of cancer

    Fransen, Marieke F / Cornelis J.M. Melief / Ferry Ossendorp / Jan W. Drijfhout / Marjolein Sluijter / Mies J. van Steenbergen / Robert A. Cordfunke / Wim E. Hennink

    Vaccine. 2014 Mar. 26, v. 32, no. 15

    2014  

    Abstract: Slow-release delivery has great potential for specifically targeting immune-modulating agents into the tumor-draining area. In prior work we showed that local treatment of slowly delivered anti-CD40 antibody induced robust anti-tumor CD8+ T cell ... ...

    Abstract Slow-release delivery has great potential for specifically targeting immune-modulating agents into the tumor-draining area. In prior work we showed that local treatment of slowly delivered anti-CD40 antibody induced robust anti-tumor CD8+ T cell responses without systemic toxicity. We now report on the comparison of two slow-release delivery systems for their use in antibody-based immunotherapy of cancer. Anti-CD40 agonistic antibody delivered locally in mineral oil Montanide ISA 51 or in dextran-based microparticles activated tumor-specific T cell activation. Both slow-release formulations significantly decreased systemic side-effects compared to systemic administration of anti-CD40 antibody. However, dextran-based microparticles caused serious local inflammation associated with unwanted rapid outgrowth of tumors instead of the tumor clearance observed with delivery in Montanide. We therefore conclude that Montanide ISA 51 is to be preferred as a slow-release agent for CD40 agonist immunotherapy of cancer.
    Keywords adverse effects ; agonists ; antibodies ; CD8-positive T-lymphocytes ; immunomodulators ; immunotherapy ; inflammation ; mineral oil ; neoplasms ; toxicity ; vaccines
    Language English
    Dates of publication 2014-0326
    Size p. 1654-1660.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2014.01.056
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1930: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 458: Show issues

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  3. Article: Linking T cell epitopes to a common linear B cell epitope: A targeting and adjuvant strategy to improve T cell responses

    Mangsbo, Sara M / Erika A.K. Fletcher / Wendy W.C. van Maren / Anke Redeker / Robert A. Cordfunke / Inken Dillmann / Jasper Dinkelaar / Kahina Ouchaou / Jeroen D.C. Codee / Gijs A. van der Marel / Peter Hoogerhout / Cornelis J.M. Melief / Ferry Ossendorp / Jan W. Drijfhout

    Molecular Immunology. 2018 Jan., v. 93

    2018  

    Abstract: Immune complexes are potent mediators of cellular immunity and have been extensively studied for their disease mediating properties in humans and for their role in anti-cancer immunity. However, a viable approach to use antibody-complexed antigen as ... ...

    Abstract Immune complexes are potent mediators of cellular immunity and have been extensively studied for their disease mediating properties in humans and for their role in anti-cancer immunity. However, a viable approach to use antibody-complexed antigen as vehicle for specific immunotherapy has not yet reached clinical use. Since virtually all people have endogenous antibodies against tetanus toxoid (TTd), such commonly occurring antibodies are promising candidates to utilize for immune modulation. As an initial proof-of-concept we investigated if anti-tetanus IgG could induce potent cross-presentation of a conjugate with SIINFEKL, a MHC class I presented epitope of ovalbumin (OVA), to TTd. This protein conjugate enhanced OVA-specific CD8+ T cell responses when administrated to seropositive mice. Since TTd is poorly defined, we next investigated whether a synthetic peptide–peptide conjugate, with a chemically defined linear B cell epitope of tetanus toxin (TTx) origin, could improve cellular immune responses. Herein we identify one linear B cell epitope, here after named MTTE thru a screening of overlapping peptides from the alpha and beta region of TTx, and by assessment of the binding of pooled IgG, or individual human IgG from high-titer TTd vaccinated donors, to these peptides. Subsequently, we developed a chemical protocol to synthesize defined conjugates containing multiple copies of MTTE covalently attached to one or more T cell epitopes of choice. To demonstrate the potential of the above approach we showed that immune complexes of anti-MTTE antibodies with MTTE-containing conjugates are able to induce DC and T cell activation using model antigens.
    Keywords B-lymphocytes ; CD8-positive T-lymphocytes ; adjuvants ; antibodies ; antigen-antibody complex ; cell-mediated immunity ; chemical bonding ; conjugated proteins ; epitopes ; humans ; immunoglobulin G ; immunomodulation ; immunotherapy ; mice ; models ; ovalbumin ; people ; peptides ; screening ; seroprevalence ; tetanus
    Language English
    Dates of publication 2018-01
    Size p. 115-124.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 424427-8
    ISSN 1872-9142 ; 0161-5890
    ISSN (online) 1872-9142
    ISSN 0161-5890
    DOI 10.1016/j.molimm.2017.11.004
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 166: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Human papillomavirus deregulates the response of a cellular network comprising of chemotactic and proinflammatory genes.

    Rezaul Karim / Craig Meyers / Claude Backendorf / Kristina Ludigs / Rienk Offringa / Gert-Jan B van Ommen / Cornelis J M Melief / Sjoerd H van der Burg / Judith M Boer

    PLoS ONE, Vol 6, Iss 3, p e

    2011  Volume 17848

    Abstract: Despite the presence of intracellular pathogen recognition receptors that allow infected cells to attract the immune system, undifferentiated keratinocytes (KCs) are the main targets for latent infection with high-risk human papilloma viruses (hrHPVs). ... ...

    Abstract Despite the presence of intracellular pathogen recognition receptors that allow infected cells to attract the immune system, undifferentiated keratinocytes (KCs) are the main targets for latent infection with high-risk human papilloma viruses (hrHPVs). HPV infections are transient but on average last for more than one year suggesting that HPV has developed means to evade host immunity. To understand how HPV persists, we studied the innate immune response of undifferentiated human KCs harboring episomal copies of HPV16 and 18 by genome-wide expression profiling. Our data showed that the expression of the different virus-sensing receptors was not affected by the presence of HPV. Poly(I:C) stimulation of the viral RNA receptors TLR3, PKR, MDA5 and RIG-I, the latter of which indirectly senses viral DNA through non-self RNA polymerase III transcripts, showed dampening in downstream signalling of these receptors by HPVs. Many of the genes downregulated in HPV-positive KCs involved components of the antigen presenting pathway, the inflammasome, the production of antivirals, pro-inflammatory and chemotactic cytokines, and components downstream of activated pathogen receptors. Notably, gene and/or protein interaction analysis revealed the downregulation of a network of genes that was strongly interconnected by IL-1β, a crucial cytokine to activate adaptive immunity. In summary, our comprehensive expression profiling approach revealed that HPV16 and 18 coordinate a broad deregulation of the keratinocyte's inflammatory response, and contributes to the understanding of virus persistence.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2011-03-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Human papillomavirus (HPV) upregulates the cellular deubiquitinase UCHL1 to suppress the keratinocyte's innate immune response.

    Rezaul Karim / Bart Tummers / Craig Meyers / Jennifer L Biryukov / Samina Alam / Claude Backendorf / Veena Jha / Rienk Offringa / Gert-Jan B van Ommen / Cornelis J M Melief / Daniele Guardavaccaro / Judith M Boer / Sjoerd H van der Burg

    PLoS Pathogens, Vol 9, Iss 5, p e

    2013  Volume 1003384

    Abstract: Persistent infection of basal keratinocytes with high-risk human papillomavirus (hrHPV) may cause cancer. Keratinocytes are equipped with different pattern recognition receptors (PRRs) but hrHPV has developed ways to dampen their signals resulting in ... ...

    Abstract Persistent infection of basal keratinocytes with high-risk human papillomavirus (hrHPV) may cause cancer. Keratinocytes are equipped with different pattern recognition receptors (PRRs) but hrHPV has developed ways to dampen their signals resulting in minimal inflammation and evasion of host immunity for sustained periods of time. To understand the mechanisms underlying hrHPV's capacity to evade immunity, we studied PRR signaling in non, newly, and persistently hrHPV-infected keratinocytes. We found that active infection with hrHPV hampered the relay of signals downstream of the PRRs to the nucleus, thereby affecting the production of type-I interferon and pro-inflammatory cytokines and chemokines. This suppression was shown to depend on hrHPV-induced expression of the cellular protein ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) in keratinocytes. UCHL1 accomplished this by inhibiting tumor necrosis factor receptor-associated factor 3 (TRAF3) K63 poly-ubiquitination which lead to lower levels of TRAF3 bound to TANK-binding kinase 1 and a reduced phosphorylation of interferon regulatory factor 3. Furthermore, UCHL1 mediated the degradation of the NF-kappa-B essential modulator with as result the suppression of p65 phosphorylation and canonical NF-κB signaling. We conclude that hrHPV exploits the cellular protein UCHL1 to evade host innate immunity by suppressing PRR-induced keratinocyte-mediated production of interferons, cytokines and chemokines, which normally results in the attraction and activation of an adaptive immune response. This identifies UCHL1 as a negative regulator of PRR-induced immune responses and consequently its virus-increased expression as a strategy for hrHPV to persist.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 616
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Effective melanoma immunotherapy in mice by the skin-depigmenting agent monobenzone and the adjuvants imiquimod and CpG.

    Jasper G van den Boorn / Debby Konijnenberg / Esther P M Tjin / Daisy I Picavet / Nico J Meeuwenoord / Dmitri V Filippov / J P Wietze van der Veen / Jan D Bos / Cornelis J M Melief / Rosalie M Luiten

    PLoS ONE, Vol 5, Iss 5, p e

    2010  Volume 10626

    Abstract: Presently melanoma still lacks adequate treatment options for metastatic disease. While melanoma is exceptionally challenging to standard regimens, it is suited for treatment with immunotherapy based on its immunogenicity. Since treatment-related skin ... ...

    Abstract Presently melanoma still lacks adequate treatment options for metastatic disease. While melanoma is exceptionally challenging to standard regimens, it is suited for treatment with immunotherapy based on its immunogenicity. Since treatment-related skin depigmentation is considered a favourable prognostic sign during melanoma intervention, we here aimed at the reverse approach of directly inducing vitiligo as a shortcut to effective anti-melanoma immunity.We developed an effective and simple to use form of immunotherapy by combining the topical skin-bleaching agent monobenzone with immune-stimulatory imiquimod cream and cytosine-guanine oligodeoxynucleotides (CpG) injections (MIC therapy). This powerful new approach promptly induced a melanoma antigen-specific immune response, which abolished subcutaneous B16.F10 melanoma growth in up to 85% of C57BL/6 mice. Importantly, this regimen induced over 100 days of tumor-free survival in up to 60% of the mice, and forcefully suppressed tumor growth upon re-challenge either 65- or 165 days after MIC treatment cessation.MIC therapy is effective in eradicating melanoma, by vigilantly incorporating NK-, B- and T cells in its therapeutic effect. Based on these results, the MIC regimen presents a high-yield, low-cost and simple therapy, readily applicable in the clinic.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2010-05-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Correction

    Carmen Elena Gómez / Beatriz Perdiguero / Victoria Jiménez / Abdelali Filali-Mouhim / Khader Ghneim / Elias K. Haddad / Esther D. Quakkerlaar / Julie Delaloye / Alexandre Harari / Thierry Roger / Thomas Duhen / Rafick P. Sékaly / Cornelis J. M. Melief / Thierry Calandra / Federica Sallusto / Antonio Lanzavecchia / Ralf Wagner / Giuseppe Pantaleo / Mariano Esteban

    PLoS ONE, Vol 7, Iss

    Systems Analysis of MVA-C Induced Immune Response Reveals Its Significance as a Vaccine Candidate against HIV/AIDS of Clade C.

    2012  Volume 9

    Keywords Medicine ; R ; Science ; Q
    Language English
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Correction

    Carmen Elena Gómez / Beatriz Perdiguero / Victoria Jiménez / Abdelali Filali-Mouhim / Khader Ghneim / Elias K. Haddad / Esther D. Quakkerlaar / Julie Delaloye / Alexandre Harari / Thierry Roger / Thomas Dunhen / Rafick P. Sékaly / Cornelis J. M. Melief / Thierry Calandra / Federica Sallusto / Antonio Lanzavecchia / Ralf Wagner / Giuseppe Pantaleo / Mariano Esteban

    PLoS ONE, Vol 7, Iss

    Systems Analysis of MVA-C Induced Immune Response Reveals Its Significance as a Vaccine Candidate against HIV/AIDS of Clade C

    2012  Volume 5

    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Correction

    Carmen Elena Gómez / Beatriz Perdiguero / Victoria Jiménez / Abdelali Filali-Mouhim / Khader Ghneim / Elias K. Haddad / Esther D. Quakkerlaar / Julie Delaloye / Alexandre Harari / Thierry Roger / Thomas Duhen / Rafick P. Sékaly / Cornelis J. M. Melief / Thierry Calandra / Federica Sallusto / Antonio Lanzavecchia / Ralf Wagner / Giuseppe Pantaleo / Mariano Esteban

    PLoS ONE, Vol 7, Iss

    Systems Analysis of MVA-C Induced Immune Response Reveals Its Significance as a Vaccine Candidate against HIV/AIDS of Clade C

    2012  Volume 9

    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

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  10. Article ; Online: Correction

    Carmen Elena Gómez / Beatriz Perdiguero / Victoria Jiménez / Abdelali Filali-Mouhim / Khader Ghneim / Elias K. Haddad / Esther D. Quakkerlaar / Julie Delaloye / Alexandre Harari / Thierry Roger / Thomas Dunhen / Rafick P. Sékaly / Cornelis J. M. Melief / Thierry Calandra / Federica Sallusto / Antonio Lanzavecchia / Ralf Wagner / Giuseppe Pantaleo / Mariano Esteban

    PLoS ONE, Vol 7, Iss

    Systems Analysis of MVA-C Induced Immune Response Reveals Its Significance as a Vaccine Candidate against HIV/AIDS of Clade C.

    2012  Volume 5

    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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