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Angela Krackhardt - Translational Immunotherapie
My overall research goal is the development of novel cancer immunotherapies focusing especially on adoptive transfer of tumor-reactive T cells. We are highly interested in the identification of major histocompatibility complex (MHC)-associated peptide ligands exclusively presented by tumor cells and therefore highly suitable for specific tumor rejection. Therefore, we have pioneered experimental proteogenomic workflows based on personalized deep sequencing and mass spectrometry data allowing the sensitive detection of such neoantigens. We additionally perform in-depth analyses of tumor-reactive T-cell receptors (TCR) and investigate their reactivity patterns in vitro and in vivo in order to define qualities necessary for robust and sustainable anti-tumor reactivity. We apply and combine personalized multiomics analyses to characterize individual immune-associated key determinants related to response to immunotherapy as well as survival, a project which has been funded as a joint funding project by the DKTK. Taking a systemic immunological perspective, we aim to understand cross disease patterns of tumor immunology which may lead to novel biomarkers or key regulators of the tumor microenvironment. We are additionally working on clinically translatable novel imaging strategies to track anti-tumor reactive T cells in vivo.
We understand clinical translation as continuous learning process between preclinical and clinical research in order to provide the highest patient care and foster the development of innovative treatment options for our patients.
Angela Krackhardt studied Medicine from 1989 to 1996 in Berlin and subsequently worked as clinician scientist at the Charité. She finished her MD thesis in 1998 in the field of tumor immunology. In 1999, she went for a postdoc to the Dana Farber Cancer Institute in Boston and became Instructor in Oncology in 2001. In 2002, she moved back to Berlin to continue her clinical training. In 2005, she moved to Munich to start her own junior research group “Adoptine T cell therapy” at the Institute of Molecular Immunology, Helmholtz Zentrum München. In 2010, she became appointed as W2 professor of Translational Immunotherapy at the TU München, where she is heading a research group. Since then, she also continued her clinical work at the IIIrd Medical Department, Hematology and Oncology, of the Klinikum rechts der Isar. She is a certified specialist of Internal Medicine, Hematology and Oncology and works as senior physician and attending. In addition she is the Head of Specific Cellular Therapy Program of the IIIrd Medical Department, Hematology and Oncology, of the Klinikum rechts der Isar.
- Appointment to scientific advisory group at EMA (2021)
- Scientific Advisory Board Immune Image (2019)
- Faculty Board of the PhD Graduate Program, Faculty of Medicine TUM (2019)
- Faculty Board of the Graduate Program Translational Medicine, Faculty of Medicine TUM (2015)
- Scientific advisory council of the IZKF, Julius-Maximilians-Universität Würzburg (2012)
- BayImmuNet Research Project Group Award (Bayerisches Staatsministerium für Wissenschaft, Forschung und Kunst) (2008)
- Life Science Foundation Research Award (HMGU, Munich, Germany) (2005)
- Postdoc-Stipendium der Deutschen Krebshilfe (1999)
Braunlein, E., Lupoli, G., Fuchsl, F., Abualrous, E.T., de Andrade Kratzig, N., Gosmann, D., Wietbrock, L., Lange, S., Engleitner, T., Lan, H., Audehm, S., Effenberger, M., Boxberg, M., Steiger, K., Chang, Y., Yu, K., Atay, C., Bassermann, F., Weichert, W., Busch, D.H., Rad, R., Freund, C., Antes, I., and Krackhardt, A.M. (2021). Functional analysis of peripheral and intratumoral neoantigen-specific TCRs identified in a patient with melanoma. J Immunother Cancer 9.
Audehm, S., Glaser, M., Pecoraro, M., Braunlein, E., Mall, S., Klar, R., Effenberger, M., Albers, J., Bianchi, H.O., Peper, J., Yusufi, N., Busch, D.H., Stevanovic, S., Mann, M., Antes, I., and Krackhardt, A.M. (2019). Key Features Relevant to Select Antigens and TCR From the MHC-Mismatched Repertoire to Treat Cancer. Front Immunol 10, 1485.
Krackhardt, A.M., Anliker, B., Hildebrandt, M., Bachmann, M., Eichmuller, S.B., Nettelbeck, D.M., Renner, M., Uharek, L., Willimsky, G., Schmitt, M., Wels, W.S., and Schussler-Lenz, M. (2018). Clinical translation and regulatory aspects of CAR/TCR-based adoptive cell therapies-the German Cancer Consortium approach. Cancer Immunol Immunother 67, 513-523.
Mayer, K.E., Mall, S., Yusufi, N., Gosmann, D., Steiger, K., Russelli, L., Bianchi, H.O., Audehm, S., Wagner, R., Braunlein, E., Stelzl, A., Bassermann, F., Weichert, W., Weber, W., Schwaiger, M., D'Alessandria, C., and Krackhardt, A.M. (2018). T-cell functionality testing is highly relevant to developing novel immuno-tracers monitoring T cells in the context of immunotherapies and revealed CD7 as an attractive target. Theranostics 8, 6070-6087.
Bassani-Sternberg, M., Braunlein, E., Klar, R., Engleitner, T., Sinitcyn, P., Audehm, S., Straub, M., Weber, J., Slotta-Huspenina, J., Specht, K., Martignoni, M.E., Werner, A., Hein, R., D, H.B., Peschel, C., Rad, R., Cox, J., Mann, M., and Krackhardt, A.M. (2016). Direct identification of clinically relevant neoepitopes presented on native human melanoma tissue by mass spectrometry. Nat Commun 7, 13404.
Mall, S., Yusufi, N., Wagner, R., Klar, R., Bianchi, H., Steiger, K., Straub, M., Audehm, S., Laitinen, I., Aichler, M., Peschel, C., Ziegler, S., Mustafa, M., Schwaiger, M., D'Alessandria, C., and Krackhardt, A.M. (2016). Immuno-PET Imaging of Engineered Human T Cells in Tumors. Cancer Res 76, 4113-4123.
Klar, R., Schober, S., Rami, M., Mall, S., Merl, J., Hauck, S.M., Ueffing, M., Admon, A., Slotta-Huspenina, J., Schwaiger, M., Stevanovic, S., Oostendorp, R.A., Busch, D.H., Peschel, C., and Krackhardt, A.M. (2014). Therapeutic targeting of naturally presented myeloperoxidase-derived HLA peptide ligands on myeloid leukemia cells by TCR-transgenic T cells. Leukemia 28, 2355-2366.
Weigand, L.U., Liang, X., Schmied, S., Mall, S., Klar, R., Stotzer, O.J., Salat, C., Gotze, K., Mautner, J., Peschel, C., and Krackhardt, A.M. (2012). Isolation of human MHC class II-restricted T cell receptors from the autologous T-cell repertoire with potent anti-leukaemic reactivity. Immunology 137, 226-238.
Schuster, I.G., Busch, D.H., Eppinger, E., Kremmer, E., Milosevic, S., Hennard, C., Kuttler, C., Ellwart, J.W., Frankenberger, B., Nossner, E., Salat, C., Bogner, C., Borkhardt, A., Kolb, H.J., and Krackhardt, A.M. (2007). Allorestricted T cells with specificity for the FMNL1-derived peptide PP2 have potent antitumor activity against hematologic and other malignancies. Blood 110, 2931-2939.
Krackhardt, A.M., Witzens, M., Harig, S., Hodi, F.S., Zauls, A.J., Chessia, M., Barrett, P., and Gribben, J.G. (2002). Identification of tumor-associated antigens in chronic lymphocytic leukemia by SEREX. Blood 100, 2123-2131.