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Immune-related effects of Hyperthermia

Molecular Hyperthermia

Supraphysiological heating (lat.: hyperthermia) is one of the oldest methods for the treatment of degenerated cells and was first mentioned around 5000 BC. Significant technical advances in the field of radiofrequency applicators (13.45 MHz to 2.45 GHz) and non-invasive MR thermometry led from the 1970s onwards to the fact that hyperthermia can also be used in the targeted treatment of tumors. During hyperthermia treatment, the tumor is heated once or twice a week to a target temperature between 39 °C and 45 °C for approximately 60 minutes. If clinical hyperthermia is responsibly prescribed, carefully administered, and fully documented in its effects and side effects, it can lead to significant improvements at various levels. However, the latter is only successful if hyperthermia is used in the form of a multimodal treatment, i.e. in combination with radio(chemo)therapy and, if necessary, immunotherapy. 

The molecular hyperthermia aims the elucidation of fundamental immunobiological and physical mechanisms that take place during hyperthermia and in the context of combination treatments. To study basic heating effects outside the organism (ex vivo), the group has heating chambers and partly self-developed radiative (microwave) systems that closely resemble clinical hyperthermia. In order to investigate immunobiological heating effects also within the body (in vivo), the working group also conducts small animal experiments with mice in compliance with animal welfare regulations. Methods such as multicolor flow cytometry, (multispot)ELISA, western blot, real time qPCR, histology and MR-/PET-CT imaging allow detailed investigation and characterization. Technical developments usually take place in cooperation with leading medical technology companies from the field of clinical hyperthermia, whereby (pre)clinical issues are always taken into account.

Strahlenklinik

Prof. Dr. rer. nat. habil. Udo Gaipl

E-mail: udo.gaipl(at)uk-erlangen.de

Strahlenklinik

Dr. rer. nat. Michael Rückert

E-mail: michael.rueckert(at)uk-erlangen.de

Strahlenklinik

Azzaya Sengedorj M. Sc.

E-mail: azzaya.sengedorj(at)uk-erlangen.de

Strahlenklinik

Rupali Khatun M. Sc.

E-mail: rupali.khatun(at)uk-erlangen.de

Strahlenklinik

Benjamin Kahlert M. Sc.

E-mail: benjamin.kahlert(at)extern.uk-erlangen.de

Selected publications

Rationale of hyperthermia
Hader, M.; Frey, B.; Fietkau, R.; et al. Immune biological rationales for the design of combined radio- and immunotherapies. Cancer Immunol Immunother; 2020, 69, 293–306 doi.org/10.1007/s00262-019-02460-3

Preclinical hyperthermia
Hader, M.; Savcigil, D.P.; Rosin, A.; Ponfick, P.; Gekle, S.; Wadepohl, M.; Bekeschus, S.; Fietkau, R.; Frey, B.; Schlücker, E.; Gaipl, U.S. Differences of the Immune Phenotype of Breast Cancer Cells after Ex Vivo Hyperthermia by Warm-Water or Microwave Radiation in a Closed-Loop System Alone or in Combination with Radiotherapy; Cancers; 2020, 12, 1082. https://doi.org/10.3390/cancers12051082

Rosin, A.; Hader, M.; Drescher, C.; Suntinger, M.; Gerdes, T.; Willert-Porada, M.; Gaipl, U. S.; Frey, B. Comparative study and simulation of tumor cell inactivation by microwave and conventional heating.
COMPEL : The International Journal for Computation and Mathematics in Electrical and Electronic Engineering; 2018, 37 (6) . 1893-1904. doi.org/10.1108/COMPEL-03-2017-0144

Werthmöller, N.; Frey, B.; Rückert, M.; Lotter, M.; Fietkau, R.; Gaipl, U.S. Combination of ionising radiation with hyperthermia increases the immunogenic potential of B16-F10 melanoma cells in vitro and in vivo. Int J Hyperthermia. 2016; 32(1):23-30.

Schildkopf, P.; Frey, B.; Ott, O.J.; Rubner, Y.; Multhoff, G.; Sauer, R; Fietkau, R.; Gaipl U.S. Radiation combined with hyperthermia induces HSP70-dependent maturation of dendritic cells and release of pro-inflammatory cytokines by dendritic cells and macrophages. Radiother Oncol. 2011 Oct;101(1):109-15. doi.org/10.1016/j.radonc.2011.05.056

Clinical hyperthermia
Datta, N.R.; Kok, H.P.; Crezee, H.; Gaipl, U.S.; and Bodis, S.: Integrating Loco-Regional Hyperthermia Into the Current Oncology Practice: SWOT and TOWS Analyses. Front. Oncol. 2020, 10:819.  doi.org/10.3389/fonc.2020.00819

Project-related third party funding

Bayerische Forschungsstiftung:
Multiskalenuntersuchung der Hyperthermie für neue additive Tumorbehandlungsstrategien (Microthermia)

European Union Horizon 2020 (HYPERBOOST):
ESR4- UKER: Elucidate the effects and reveal mechanisms of hyperthermia in combination with radiotherapy on the innate and adaptive immune system in pre-clinical model systems
ESR11-UKER: Monitoring immune effects of hyperthermia in multimodal settings with radiotherapy in patients and definition of prognostic and predictive markers

Cooperation partner

Dipl.-Ing. Martin Wadepohl (Dr. Sennewald Medizintechnik)