Research Group Mocikat
Regulation of innate and adaptive immunity as the basis for new approaches of immunotherapy
Research interests
Our research group studies immunological aspects of hematological neoplasias, i.e. leukemias and lymphomas. In our research we are pursuing two objectives:
With reference to knowledge-oriented basic research, we are seeking to elucidate the mechanisms that underlie immune response regulation. Hematological tumors are used as a model system to answer the question how an immune response against malignant cells can arise and through which mechanisms these evade an attack by immunological effector cells. The investigations focus on the complex interactions between antigen-presenting cells, natural killer cells, T lymphocytes and tumor cells.
In a translational approach the results of basic research shall be made applicable for use in the clinic. Because leukemias and lymphomas are common diseases and – despite recent progress in radiotherapy and chemotherapy – still have an unfavorable prognosis, the development of new therapy strategies is urgently needed. After it has become clear that the immune system is able in principle to detect malignant cells, the targeted manipulation of immunological effector systems could be an appropriate therapy approach. This shall take place through the transfer of immune cells (T lymphocytes, natural killer cells, antigen-presenting cells) or through vaccination. For vaccination, tumor cells could be used that have been genetically modified.
The outlined research problems are being studied both in vitro in cell culture systems and also in vivo in preclinical models. The entanglement of knowledge-oriented and application-oriented approaches is reflected in the extensive arsenal of methods, which includes molecular biological, cell biological, immunological and in vivo techniques. Access to clinical material is of great significance; this is ensured through cooperations with institutions of the Klinikum Großhadern.
Figure: Vaccination with trioma cells is a new potent vaccination approach against malignant B cell lymphomas. Triomas are generated by the fusion of tumor cells with hybridomas, which express an immunoglobulin directed against internalizing and activating surface molecules on antigen-presenting cells. The redirection of trioma cells with the enclosed lymphoma-derived antigens against these receptors leads to an efficient protective T cell response. Since the trioma cells contain potentially all (also not yet known) tumor-associated antigens, this results in a polyvalent response, which makes an immune evasion of the tumor more difficult. The yellow color of the chromosome components in this image of a fluorescence in situ hybridization (FISH) shows that trioma cells, which were produced from the leukemia cells of a patient contained the DNA of this patient. The image was produced in cooperation with Dr. Gangnus.
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Contact Address
| Prof. Dr. med. Ralph Mocikat | |
|---|---|
| Office: | +49(0)89 7099 -313 |
| Labs: | +49(0)89 7099 -309 and -310 |
| Fax: | +49(0)89 7099 -300 |
| Email: | mocikat@helmholtz-muenchen.de |
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Staff
Prof. Dr. med. Ralph Mocikat (Group Leader)
Margarethe Przewoznik (PhD student)
Marcella Naujoks (PhD student)
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Publications
Further publications:
Mocikat, R.
Hoch-effiziente Expression chimärisierter anti-T-Zell-Antikörper für die präklinische Evaluierung der immunsuppressiven Effektorfunktionen humaner Isotypen in vivo.
Habilitationsschrift, Ludwig-Maximilians-Universität München (1994).
Mocikat, R. und Thierfelder, S.
Gentechnisch modifizierte Antikörper für die Tumorimmuntherapie.
Die Medizinische Welt 48, 169-175 (1997).
Müller, K.M., Arndt K.M., Bauer K. und Plückthun, A.
Tandem immobilized metal-ion affinity chromatography/immunoaffinity purification of His-tagged proteins - evaluation of two anti-His-tag monoclonal antibodies.
Anal. Biochem. 259, 54-61 (1998).
Mocikat, R., Selmayr, M., Strehl, J., Dieckmann, A., Thierfelder, S. und Lindhofer, H.
Targeting of antigen processing mechanisms for tumor therapy.
IBST 11, 114-118 (1998).
Schröder, T., Lange, C., Strehl, J. und Just, U.
Generation of functionally mature dendritic cells from the multipotential stem cell line FDCP-mix.
Br. J. Haematol. 111, 890-897 (2000).
Mocikat, R., Egeter., O. und Röcken, M.
Heilung von B-Zell-Lymphomen durch Transfer von T-Helfer-Zellen.
Jahresbericht der GSF 1999. München, 2000, S. 73-78.
Mocikat, R.
Immuntherapie der chronisch-lymphatischen Leukämie mittels Triomzell-Vakzinierung.
Jahresbericht der GSF 2001. München, 2002, S. 81-86.
Mocikat, R. und Röcken, M.
Ein neuer Pfad der Immunaktivierung.
Jahresbericht der GSF 2003. München, 2004, S. 87-90
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Theses
Lang, P.
Homologe Rekombination am Immunglobulin-Schwere-Ketten-Locus von Maus- und Ratten-Hybridomzelllinien.
Fakultät für Biologie, LMU München (1993)
Kardinal, C.
Untersuchungen zur Herstellung chimärisierter Antikörper.
Fakultät für Biologie, LMU München (1995)
Menzel, H.
Adoptive Immuntherapie im murinen Leukämie-Rezidiv-Modell nach allogener Knochenmarktransplantation.
Medizinische Fakultät, LMU München (1997)
Selmayr, M.
Vakzinierung gegen murine B-Zell-Lymphome durch genetische Modifikation des Immunglobulin-Idiotyps.
Fakultät für Chemie und Pharmazie, LMU München (1998)
Strehl, J.
Vakzinierung gegen murine B-Zell-Lymphome mit Zytokin-Gen-modifizierten Zellen.
Medizinische Fakultät, LMU München (2001)
Kronenberger, K.
Studien zur Spezifität und Klonalität von tumorreaktiven T-Zellen aus Triom-immunisierten Mäusen.
Fakultät für Biologie, LMU München (2002)
Hellebrand, E.
Entwicklung von GM-CSF-produzierenden EBV-Vektoren für die Immuntherapie der chronisch-lymphatischen B-Zell-Leukämie.
Fakultät für Biologie, LMU München (2003)
Graf, N.
Untersuchungen zu Mechanismen der Triomzell-induzierten Tumorabstoßung.
Medizinische Fakultät, LMU München (2003)
Adam, C.
Untersuchungen zur Antitumor-Immunisierung mittels dendritischer Zellen in einem murinen Lymphommodell.
Medizinische Fakultät, LMU München (2005)
Lüking, C.
Analyse spezifischer T-Zellen in einem murinen Tumor-Immunisierungsmodell.
Fakultät für Chemie und Pharmazie, LMU München (2005)
Allgeier, T.
Tumor-Hybridzellen zur Vakzinierung bei chronischer lymphatischer B-Zell-Leukämie.
Medizinische Fakultät, LMU München (2007)
Brenner, C.
Untersuchungen zur Bedeutung von Natürlichen Killerzellen und T-Zellen in einem murinen Spontan-Tumormodell.
Fakultät für Chemie und Pharmazie, LMU München (2010)
Naujoks, M.
Untersuchungen zur Funktion von dendritischen Zellen in einem murinen Spontan-Tumormodell.
Medizinische Fakultät, LMU München (2011)
Przewoznik, M.
Phänotypische und funktionelle Charakterisierung von natürlichen Killerzellen in einem murinen Spontan-Tumormodell.
Medizinische Fakultät, LMU München (2011)
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