Studien und Forschung

Die Medizinische Klinik V nimmt als Teil des Onkologischen Zentrums an nationalen und internationalen klinischen Studien teil. Die Therapie von Patienten im Rahmen hochwertiger Studien führt zu einer hohen Behandlungsqualität und garantiert unseren Patienten den Zugang zu den modernsten Medikamenten. Höchste wissenschaftliche und insbesondere ethische Standards sind entscheidende Kennzeichen der von uns ausgewählten Studien. Voraussetzung für die Studienteilnahme ist nach eingehender Aufklärung des Patienten und angemessener Bedenkzeit die schriftliche Einverständniserklärung.

Die Koordination und Dokumentation erfolgt durch das Interdisziplinäre Studienteam des Klinikums (LINK). Im Rahmen von Studie ist es uns möglich, Ihnen Therapiekonzepte mit innovativen Medikamenten zu anzubieten. Die Besprechung von Patienten in der Interdisziplinären Tumorkonferenz ermöglicht es, dass Patienten auch an Studien mit interdisziplinären Therapiekonzepten teilnehmen können.


Aktuelle Studienübersicht


Ausgewählte Publikationen

Fusion of PDGFRB to MPRIP, CPSF6, and GOLGB1 in three patients with eosinophilia-associated myeloproliferative neoplasms. Naumann N, Schwaab J, Metzgeroth G, Jawhar M, Haferlach C, Göhring G, Schlegelberger B, Dietz CT, Schnittger S, Lotfi S, Gärtner M, Dang TA, Hofmann WK, Cross NC, Reiter A, Fabarius A. Genes Chromosomes Cancer. 2015 Sep 10. doi: 10.1002/gcc.22287. [Epub ahead of print]

A high-throughput RNAi screen for detection of immune-checkpoint molecules that mediate tumor resistance to cytotoxic T lymphocytes. <http:>Khandelwal N, Breinig M, Speck T, Michels T, Kreutzer C, Sorrentino A, Sharma AK, Umansky L, Conrad H, Poschke I, Offringa R, König R, Bernhard H, Machlenkin A, Boutros M, Beckhove P. EMBO Mol Med. 2015 Feb 17;7(4):450-63. doi: 10.15252/emmm.201404414.

Long-term complete remission following radiosurgery and immunotherapy in a melanoma patient with brain metastasis: immunologic correlates. Karbach J, Gnjatic S, Biskamp M, Atmaca A, Weidmann E, Brandt K, Wahle C, Bernhard H, Knuth A, Jäger E. Cancer Immunol Res. 2014 May;2(5):404-9. doi: 10.1158/2326-6066.CIR-13-0200. Epub 2014 Feb 5.

Transcatheter arterial chemoembolization (TACE) of colorectal cancer liver metastases by irinotecan-eluting microspheres in a salvage patient population. Huppert P, Wenzel T, Wietholtz H. Cardiovasc Intervent Radiol. 2014 Feb;37(1):154-64. doi: 10.1007/s00270-013-0632-0. Epub 2013 May 14.

Plasticity in the contribution of T cell receptor variable region residues to binding of peptide-HLA-A2 complexes. Smith SN, Sommermeyer D, Piepenbrink KH, Blevins SJ, Bernhard H, Uckert W, Baker BM, Kranz DM.J Mol Biol. 2013 Nov 15;425(22):4496-507. doi: 10.1016/j.jmb.2013.08.007. Epub 2013 Aug 14.

HLA Class II tetramers reveal tissue-specific regulatory T cells that suppress T-cell responses in breast carcinoma patients. Schmidt HH, Ge Y, Hartmann FJ, Conrad H, Klug F, Nittel S, Bernhard H, Domschke C, Schuetz F, Sohn C, Beckhove P. Oncoimmunology. 2013 Jun 1;2(6):e24962. Epub 2013 May 15.

Tumor cells in multiple myeloma patients inhibit myeloma-reactive T cells through carcinoembryonic antigen-related cell adhesion molecule-6. Witzens-Harig M, Hose D, Jünger S, Pfirschke C, Khandelwal N, Umansky L, Seckinger A, Conrad H, Brackertz B, Rème T, Gueckel B, Meißner T, Hundemer M, Ho AD, Rossi JF, Neben K, Bernhard H, Goldschmidt H, Klein B, Beckhove P. Blood. 2013 May 30;121(22):4493-503. doi: 10.1182/blood-2012-05-429415. Epub 2013 Apr 19.

A randomised multicentre phase II study with cisplatin/docetaxel vs oxaliplatin/docetaxel as first-line therapy in patients with advanced or metastatic non-small cell lung cancer. Atmaca A, Al-Batran SE, Werner D, Pauligk C, Güner T, Koepke A, Bernhard H, Wenzel T, Banat AG, Brueck P, Caca K, Prasnikar N, Kullmann F, Günther Derigs H, Koenigsmann M, Dingeldein G, Neuhaus T, Jäger E. Br J Cancer. 2013 Feb 5;108(2):265-70. doi: 10.1038/bjc.2012.555. Epub 2013 Jan 17.

NY-ESO-1 antigen-reactive T cell receptors exhibit diverse therapeutic capability. Sommermeyer D, Conrad H, Krönig H, Gelfort H, Bernhard H, Uckert W. Int J Cancer. 2013 Mar 15;132(6):1360-7. doi: 10.1002/ijc.27792. Epub 2012 Sep 14.

The efficiency of human cytomegalovirus pp65(495-503) CD8+ T cell epitope generation is determined by the balanced activities of cytosolic and endoplasmic reticulum-resident peptidases. Urban S, Textoris-Taube K, Reimann B, Janek K, Dannenberg T, Ebstein F, Seifert C, Zhao F, Kessler JH, Halenius A, Henklein P, Paschke J, Cadel S, Bernhard H, Ossendorp F, Foulon T, Schadendorf D, Paschen A, Seifert U. J Immunol. 2012 Jul 15;189(2):529-38. doi: 10.4049/jimmunol.1101886. Epub 2012 Jun 15.

PD-1 expression on Melan-A-reactive T cells increases during progression to metastatic disease. Krönig H, Julia Falchner K, Odendahl M, Brackertz B, Conrad H, Muck D, Hein R, Blank C, Peschel C, Haller B, Schulz S, Bernhard H. Int J Cancer. 2012 May 15;130(10):2327-36. doi: 10.1002/ijc.26272. Epub 2012 Jan 11.

Specific recognition and inhibition of Ewing tumour growth by antigen-specific allo-restricted cytotoxic T cells. Thiel U, Pirson S, Müller-Spahn C, Conrad H, Busch DH, Bernhard H, Burdach S, Richter GH. Br J Cancer. 2011 Mar 15;104(6):948-56. doi: 10.1038/bjc.2011.54. Erratum in: Br J Cancer. 2011 Aug 9;105(4):596.

FLT3-regulated antigens as targets for leukemia-reactive cytotoxic T lymphocytes. Brackertz B, Conrad H, Daniel J, Kast B, Krönig H, Busch DH, Adamski J, Peschel C, Bernhard H. Blood Cancer J. 2011 Mar;1(3):e11. doi: 10.1038/bcj.2011.12. Epub 2011 Mar 18.

Targeting the epidermal growth factor receptor (HER) family by T cell receptor gene-modified T lymphocytes. Meyerhuber P, Conrad H, Stärck L, Leisegang M, Busch DH, Uckert W, Bernhard H. J Mol Med. 2010 Nov;88(11):1113-21. Epub 2010 Aug 11.

Allorestricted T lymphocytes with a high avidity T-cell receptor towards NY-ESO-1 have potent anti-tumor activity. Krönig H, Hofer K, Conrad H, Guilaume P, Müller J, Schiemann M, Lennerz V, Cosma A, Peschel C, Busch DH, Romero P, Bernhard H. Int J Cancer. 2009 Aug 1;125(3):649-55.

Use of tumour-responsive T cells as cancer treatment. Disis ML, Bernhard H, Jaffee EM. Lancet. 2009 Feb 21;373(9664):673-83. Review. Huebner G, Link H, Kohne CH, Stahl M, Kretzschmar A, Steinbach S, Folprecht G, Bernhard H, Al-Batran SE, Schoffski P, Burkart C, Kullmann F, Otremba B, Menges M, Hoffmann M, Kaiser U, Aldaoud A, Jahn A; German CUP Study Group.

Paclitaxel and carboplatin vs gemcitabine and vinorelbine in patients with adeno- or undifferentiated carcinoma of unknown primary: a randomised prospective phase II trial. Br J Cancer. 2009 Jan 13;100(1):44-9. doi: 10.1038/sj.bjc.6604818. Epub 2008 Dec 9.

CTLs directed against HER2 specifically cross-react with HER3 and HER4. Conrad H, Gebhard K, Krönig H, Neudorfer J, Busch DH, Peschel C, Bernhard H. J Immunol. 2008 Jun 15;180(12):8135-45.

Visualization of antigen-specific human cytotoxic T lymphocytes labeled with superparamagnetic iron-oxide particles. Beer AJ, Holzapfel K, Neudorfer J, Piontek G, Settles M, Krönig H, Peschel C, Schlegel J, Rummeny EJ, Bernhard H. Eur Radiol. 2008 Jun;18(6):1087-95. Epub 2008 Feb 20.

The immunogenicity of Bcr-Abl expressing dendritic cells is dependent on the Bcr-Abl kinase activity and dominated by Bcr-Abl regulated antigens. Scheich F, Duyster J, Peschel C, Bernhard H. Blood. 2007 Oct 1;110(7):2556-60. Epub 2007 Jun 19.

Adoptive transfer of autologous, HER2-specific, cytotoxic T lymphocytes for the treatment of HER2-overexpressing breast cancer. Bernhard H, Neudorfer J, Gebhard K, Conrad H, Hermann C, Nährig J, Fend F, Weber W, Busch DH, Peschel C.  Cancer Immunol Immunother. 2008 Feb;57(2):271-80. Epub 2007 Jul 24.Stemmler HJ, Schmitt M, Willems A, Bernhard H, Harbeck N, Heinemann V.

Ratio of trastuzumab levels in serum and cerebrospinal fluid is altered in HER2-positive breast cancer patients with brain metastases and impairment of blood-brain barrier. Anticancer Drugs. 2007 Jan;18(1):23-8.

Reversible HLA multimers (Streptamers) for the isolation of human cytotoxic T lymphocytes functionally active against tumor- and virus-derived antigens. Neudorfer J, Schmidt B, Huster KM, Anderl F, Schiemann M, Holzapfel G, Schmidt T, Germeroth L, Wagner H, Peschel C, Busch DH, Bernhard H. J Immunol Methods. 2007 Mar 30;320(1-2):119-31. Epub 2007 Jan 31. Kastenmuller W, Drexler I, Ludwig H, Erfle V, Peschel C, Bernhard H, Sutter G.

Infection of human dendritic cells with recombinant vaccinia virus MVA reveals general persistence of viral early transcription but distinct maturation-dependent cytopathogenicity. Virology. 2006 Jul 5;350(2):276-88. Epub 2006 Apr 3.

Application of intrathecal trastuzumab (Herceptintrade mark) for treatment of meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer. Stemmler HJ, Schmitt M, Harbeck N, Willems A, Bernhard H, Lässig D, Schoenberg S, Heinemann V. Oncol Rep. 2006 May;15(5):1373-7.

Designer T cells by T cell receptor replacement. Sommermeyer D, Neudorfer J, Weinhold M, Leisegang M, Engels B, Noessner E, Heemskerk MH, Charo J, Schendel DJ, Blankenstein T, Bernhard H, Uckert W. Eur J Immunol. 2006 Nov;36(11):3052-9.

Isolation and expansion of tumor-reactive cytotoxic T-cell clones for adoptive immunotherapy. Bernhard H, Schmidt B, Busch DH, Peschel C. Methods Mol Med. 2005;109:175-84.

A phase I vaccination study with tyrosinase in patients with stage II melanoma using recombinant modified vaccinia virus Ankara (MVA-hTyr). Meyer RG, Britten CM, Siepmann U, Petzold B, Sagban TA, Lehr HA, Weigle B, Schmitz M, Mateo L, Schmidt B, Bernhard H, Jakob T, Hein R, Schuler G, Schuler-Thurner B, Wagner SN, Drexler I, Sutter G, Arndtz N, Chaplin P, Metz J, Enk A, Huber C, Wölfel T. Cancer Immunol Immunother. 2005 May;54(5):453-67. Epub 2004 Dec 31.

Melanoma-reactive class I-restricted cytotoxic T cell clones are stimulated by dendritic cells loaded with synthetic peptides, but fail to respond to dendritic cells pulsed with melanoma-derived heat shock proteins in vitro. Fleischer K, Schmidt B, Kastenmüller W, Busch DH, Drexler I, Sutter G, Heike M, Peschel C, Bernhard H. J Immunol. 2004 Jan 1;172(1):162-9.

Phase II trial of irinotecan plus docetaxel in cisplatin-pretreated relapsed or refractory oesophageal cancer. Lordick F, von Schilling C, Bernhard H, Hennig M, Bredenkamp R, Peschel C. Br J Cancer. 2003 Aug 18;89(4):630-3.

Identification of vaccinia virus epitope-specific HLA-A*0201-restricted T cells and comparative analysis of smallpox vaccines. Drexler I, Staib C, Kastenmuller W, Stevanović S, Schmidt B, Lemonnier FA, Rammensee HG, Busch DH, Bernhard H, Erfle V, Sutter G. Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):217-22. Epub 2002 Dec 23.

Antihuman epidermal growth factor receptor 2 (HER2) monoclonal antibody trastuzumab enhances cytolytic activity of class I-restricted HER2-specific T lymphocytes against HER2-overexpressing tumor cells. Meyer zum Büschenfelde C, Hermann C, Schmidt B, Peschel C, Bernhard H. Cancer Res. 2002 Apr 15;62(8):2244-7.

Gangliosides inhibit the development from monocytes to dendritic cells. Wölfl M, Batten WY, Posovszky C, Bernhard H, Berthold F. Clin Exp Immunol. 2002 Dec;130(3):441-8.

Reversible MHC multimer staining for functional isolation of T-cell populations and effective adoptive transfer. Knabel M, Franz TJ, Schiemann M, Wulf A, Villmow B, Schmidt B, Bernhard H, Wagner H, Busch DH. Nat Med. 2002 Jun;8(6):631-7.

Vaccination against the HER-2/neu oncogenic protein. Bernhard H, Salazar L, Schiffman K, Smorlesi A, Schmidt B, Knutson KL, Disis ML. Endocr Relat Cancer. 2002 Mar;9(1):33-44. Review.

The generation of both T killer and Th cell clones specific for the tumor-associated antigen HER2 using retrovirally transduced dendritic cells. Meyer zum Büschenfelde CM, Metzger J, Hermann C, Nicklisch N, Peschel C, Bernhard H. J Immunol. 2001 Aug 1;167(3):1712-9.

Induction of strong hepatitis B virus (HBV) specific T helper cell and cytotoxic T lymphocyte responses by therapeutic vaccination in the trimera mouse model of chronic HBV infection. Böcher WO, Dekel B, Schwerin W, Geissler M, Hoffmann S, Rohwer A, Arditti F, Cooper A, Bernhard H, Berrebi A, Rose-John S, Shaul Y, Galle PR, Löhr HF, Reisner Y. Eur J Immunol. 2001 Jul;31(7):2071-9.

Generation of tumor-reactive CTL against the tumor-associated antigen HER2 using retrovirally transduced dendritic cells derived from CD34+ hemopoietic progenitor cells. Meyer zum Büschenfelde C, Nicklisch N, Rose-John S, Peschel C, Bernhard H. J Immunol. 2000 Oct 1;165(7):4133-40.

Medizinische Klinik V

Grafenstraße 9
64283 Darmstadt

Tel.: 06151 - 107 6651
Fax: 06151 - 107 6665

med5@mail.klinikum-darmstadt.de

Direktorin

Prof. Dr. med. Helga Bernhard

Tel.: 06151 - 107 6651

Onkologische und Hämatologische Ambulanz

Mo. - Do. 8.00 - 16.30 Uhr
Fr. 8.00 - 14.00 Uhr

Bleichstraße 19-21

Onkologische Ambulanz
Tel.: 06151 - 107 6657
Fax: 06151 - 107 6699

Onkologische Tagesklinik
Tel.: 06151 - 107 6672

Hotline für Niedergelassene außerhalb der Dienstzeit

Tel.: 06151 - 107 6003

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