Oncology

Krackhardt, Angela

Translational Immunotherapy - Adoptive T cell therapy

My research group is focusing on the development of novel immunotherapies in leukemia and cancer. Special focus is the identification of tumor associated antigens (TAA) preferentially presented by tumor cells as well as T cell receptors (TCR) with defined specificity for those TAA. For identification of suitable TAA the immunopeptidomic approach is followed. Specific T cells and TCR are isolated after stimulation of antigen presenting dendritic cells in the one HLA allele mismatch setting. Isolated TCR are cloned and promising candidates are intensively characterized in vitro and vivo for efficacy and potential toxicity. In addition, novel approaches as MSOT and nuclear imaging are under development in order to track TCR-transgenic T cells in vivo. The aim of my research is the clinical translation of this approach by applying adoptive T cell transfer with T cells transgenic for TCR with defined tumor reactivity in patients with refractory malignant diseases.

Selected publications:

Han Y, Yu G, Sarioglu H, Caballero-Martinez A, Schlott F, Ueffing M, Haase H, Peschel C and Krackhardt AM: Proteomic investigation of the interactome of FMNL1 in hematopoietic cells unveils a role in calcium-dependent membrane plasticity. J Proteomics 2013, 78: 72-82.

Weigand LU, Liang X, Schmied S, Mall S, Klar R, Stötzer OJ, Salat C, Götze K, Mautner J, Peschel C, Krackhardt AM: Isolation of human MHC class II-restricted TCR from the autologous T cell repertoire with potent anti-leukemic reactivity. Immunology 2012, 137: 226-238.

Höfig I, Atkinson MJ, Mall S, Krackhardt AM, Thirio C and Anastasov N (2012) Lentiviral transduction of T-cell lineage is enhanced by poloxamer synperonic F108. J Gene Med. 2012; 14:540-560.

Liang X, Weigand LU, Schuster IG, Eppinger E, van der Griendt JC, Schub A, Leisegang M, Sommermeyer D, Anderl F, Han Y, Ellwart J, Moosmann A, Busch DH, Uckert W, Peschel C, Krackhardt AM: A single T cell receptor (TCR) alpha-chain with dominant peptide recognition in the allorestricted HER2/neu-specific T cell repertoire; J. Immunol 2010; 184: 1617-1629.

Han Y, Eppinger E, Schuster IG, Weigand LU, Liang X, Kremmer E, Peschel C, Krackhardt AM: Formin-like 1 (FMNL1) is regulated by N-terminal myristoylation and induces polarized membrane blebbing; J Biol Chem 2009; 284, 33409-33417.

Schuster IG, Busch DH, Eppinger E, Kremmer E, Milosevic S, Hennard C, Kuttler C, Ellwart JW, Frankenberger B, Nößner E, Salat C, Bogner C, Borkhardt A, Kolb HJ, and Krackhardt AM: Allorestricted T cells with specificity for the FMNL1-derived peptide PP2 have potent antitumor activity against hematological and other malignancies; Blood 2007; 110: 2931-2939.