1) ICHO congress DIGITAL October 2021: Review II – Whole-Body Hyperthermia
(Review I – Superficial HT, was part of the heckelsnew 98, Nov 2021)
In the presidential session, Sharon Evans gave an excellent immunological overview on hyperthermia. Stimulating effects can be found at all steps of anti-cancer immune response, from release of cancer antigens, antigen presentation, priming and activation, trafficking of T cells and infiltration into tumors, to recognition and killing of cancer cells by T cells. The required temperatures are often in the fever range and well applicable in WBH treatment protocols.
Ralf Kleef, Wien/Budapest, presented his novel combined treatment protocol including low-dose checkpoint inhibitors , individually titrated IL-2 treatment under taurolidine protection, locoregional hyperthermia and fever-range WBH. A case series of 131 stage IV cancer patients has recently been published with encouraging efficacy and toxicity results. In this combined protocol, low-dose checkpoint inhibitors demonstrated a better safety profile without compromising the therapeutic efficacy. Kleef hypothesises that a fully activated and "de-blocked" T-cell which is further stimulated by IL-2 can perform optimal tumor cell killing if it can operate in fever mode.
There is a new interest in extreme WBH. The Belgic company ELMEDIX presented a new device "HyperTherm" using a hot air cabinet. 6 dogs bearing different tumour entities were treated under general anesthesia. It took 2,5 hours to reach 41.5°C and this temperature was kept stable for 8 hours with uniform temperature in liver, rectum, and tumour. WBH was combined with chemotherapy (simultaneously) or radiotherapy (after WBH) and overall well tolerated. Follow-up studies are in preparation. It is - as far as we know - the first approach of a long-duration extreme WBH. The ASHO award winner Xunfan Shao from Guangzhou Medical University, China, reported on clinical WBH studies. His working group has changed from applying extreme WBH with general anesthesia (41.8°C x 120min.) to WBH with deep sedation (41°C x 120min.) to fever-range WBH (FR WBH) under concious conditions (39.5 - 40.5°C x 120min.). A retrospective study using FR WBH combined with chemoradiotherapy resulted in an improved Overall Survival of patients presenting with advanced nasopharyngeal carcinoma (NPC). A clinical phase III study is in planning. In addition, they are going to carry out clinical research on WBH combined with immunotherapy for patients with metastasis from NPC.
The IOZK (Immun-Onkologisches Zentrum Köln) has developed a "Individualized Multimodal Immunotherapy" (IMI) based on personalized vaccination and including virotherapy and hyperthermia. In a retrospective analysis, reported by Stefaan van Gool, fever-range WBH (38.5 - 39.5°C, 45 - 120 min.) using heckel WBH systems, had a positive effect to restore NK cell function. The restored NK cell function was maintained during the further disease course in 36% of the patients. These positive effects were not observed in patients who did not receive WBH (most of them due to lack of time or financial ressources, not due to WBH contraindications). He concluded that WBH could be recommended as modulatory immunotherapy to support NK cell function.
Bettina Weigelin from University of Tübingen presented various effects of fever-range HT on Cytotoxic T Lymphocytes (CTL) effector function, e.g., by stabilizing CTL contacts and impairing cancer cell recovery from CTL-mediated sublethal damage. Using multiphoton intravital microscopy, the kinetics of anti-tumor immune activity can be shown in live tissue of mice. Interestingly, the immune stimulating effect of fever-range HT does only lead to a successful anti-tumor effect on the base of an activated anti-tumor response which must first be induced by other therapies, e.g., adoptive T cell therapy. However, in these combined treatment protocols, the benefitial role of fever-range HT is significant. Comparing fever-range HT of 38.5 and 39.5°C, the anti-tumor immune stimulation was interestingly quite similar. For us, the research of Bettina Weigelin and her group is a most important contribution to develop fever-range WBH as an essential module of combined treatment protocols including cytotoxic therapies and immunotherapies.
2) ESHO meeting September 14–17, 2022, in Gothenburg – congress homepage available
heckel will sponsor this important event, and we look forward to seeing you in Gothenburg!
3) STM 2022 Virtual Annual Meeting May 1 - 4, 2022
The Society for Thermal Medicine (STM) has just announced the 2022 Virtual Annual Meeting May 1 - 4, 2022. Look at the STM homepage. Abstract Submission deadline is February 1, 2022
4) New publication: 38.5°C-hyperthermia might increase the efficacy of a novel therapy using alternating electrical fields in the therapy of pancreatic cancer
5) Obituary to Dr. Ralf Kleef
Dr. Ralf Kleef (1961 – 2021) died on December, 6th, from a Covid19 infection – we lost a friend who has essentially contributed to the development of fever-range WBH in cancer treatment.
Ralf has used heckel WBH systems since 1996. Stimulated by the preclinical and clinical findings of University of Texas at Houston and Roswell Park Cancer Institute Buffalo, he routineously performed the long-duration fever-range WBH in his private out-patient clinic in Vienna, using it mainly in the adjuvant setting to decrease the risk of recurrence (see, e.g., Kleef et al 2012) and in metastatic disease where standard therapies have failed. His interest in fever-range WBH was based on appreciating infectious fever as a natural mechanism, in which the increase in body-core temperature serves as an essential trigger for initiating and controlling an extraordinary immune response. In 2001, he published a review on fever, cancer incidence and spontaneous remissions. He has always been aware that fever-range WBH can just be used as one part of a multimodular strategy. In the past years he developed a combined treatment protocol including low-dose checkpoint inhibitors, IL-2, and hyperthermia. After presenting this approach and the first case report at the 3rd Immunotherapy of Cancer Conference 2016 in Munich, he gave reports in numerous conferences, and finally published on this method by case reports (Kleef et al. 2018, Kleef et al. 2021) and by a retrospective analysis of 131 stage IV cancer patients (Kleef et al. 2020).
We miss him so much and will deeply cherish his memory.
온열치료계의 훌륭한 연구 업적들을 남기신 Ralf Kleef 박사님의 업적을 기리며, 명복을 빕니다.
※ 본 게시물은 독일 heckel gmbH.에서 발행한 뉴스레터를 전달받아 발행한 것입니다.
