Multhoff, Gabriele

Molecular Imaging. Granzyme Therapy. Cellbased Therapy

One of the focus areas of Prof. Gabriele Multhoff’s research work is the development of innovative cell-, molecule- and antibody-based targeted immunotherapies based on heat shock proteins (SFB824). The aim is to combine these new therapeutic approaches with conventional radiation therapy and chemotherapy. Her current research work has led to a randomized, multicenter clinical phase II study entitled “Targeted NK cell-based adjuvant immunotherapy for the treatment of patients with non-small cell lung carcinoma (NSCLC) after radiochemotherapy” funded by the BMBF. To stratify patients who most likely will benefit from Hsp70-targeting therapies, her group established a novel screening test (lipHsp70 ELISA, patent) to quantify liposomal, tumor-derived Hsp70 and a method to isolate circulating tumor cells (CTCs) after mesenchymal transition in the blood of patients. Liposomal Hsp70 provides a promising biomarker for viable tumor mass in different tumor entities and CTCs in the blood are presently evaluated as valuable tools for prediction of clinical responses and therapy resistance of cancer.
Her research interests also include the application of novel in vivo imaging techniques such as intraoperative, fluorescence molecular tomography (FMT), multispectral optoacoustic tomography (MSOT) and PET/CT in small animals after CT-guided irradiation of tumors using the small animal radiation research platform SARRP (DFG) and the analysis of cellular, molecular biological and immunological mechanisms in tumor and normal cells including primary endothelial cells after exposure to radiation, as well as the development of innovative nanoparticle-based theranostica.

Selected publications:

Chalmin, F., Ladoire, S., Mignot, G., Vincent, J., Bruchard, M., Remy-Martin, J. P., Boireau, W., Rouleau, A., Simon, B., Lanneau, D., De, T. A., Multhoff, G., Hamman, A., Martin, F., Chauffert, B., Solary, E., Zitvogel, L., Garrido, C., Ryffel, B., Borg, C., Apetoh, L., Rebe, C., and Ghiringhelli, F. Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells. J. Clin. Invest 120(2): 457-471, 2010.

Stangl S, Varga J, Freysoldt B, Trajkovic-Arsic M, Siveke JT, Greten FR, Ntziachristos V, Multhoff G. Selective in vivo Imaging of syngeneic, spontaneous and xenograft tumors using a novel tumor cell-specific Hsp70 peptide-based probe. Cancer Res 74(23): 6903-6912, 2014.

Stangl S, Tei L, De Rose F, Reder S, Martinelli J, Sievert W, Shevtsov M, Öllinger R, Rad R, Schwaiger M, D`Alessandria C, Multhoff G. Preclinical evaluation of the Hsp70 peptide tracer TPP-PEG24-DFO[89Zr] for tumor-specific PET/CT imaging. Cancer Res 78(21): 6268-628, doi: 10.1158/0008-5472.CAN-18-0707, 2018.

Shevtsov M, Stangl S, Nikolaev B, Yakovleva L, Marchenko Y, Tagaeva R, Sievert W, Pitkin E, Mazur A, Tolstoy P, Galibin O, Ryzhov V, Steiger K, Smirnov O, Khachatryan W, Chester K, Multhoff G. Granzyme B functionalized nanoparticles targeting membrane Hsp70-positive tumors for multimodal cancer theranostics. Small 15(13): e1900205, doi: 10.1002/smll.201900205, 2019.