Science

Thermosome is focused on targeted tumor therapy combined with immune stimulation for improved cancer treatment. Our proprietary tumor targeting concept increases local drug concentrations up to 15-fold to achieve improved clinical treatment efficacy. Combining our tumor targeting approach with regional hyperthermia elicits a measurable immune response.

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Advantages

Our technology enables actively targeted cancer therapy without the need for a specific molecular target, covering patient populations across all tumor subtypes. Thermosome´s sophisticated approach aims to improve the efficacy of tumor treatment:

  • Unmatched high levels of intra-tumoral drug concentration
  • Increased penetration depth, also reaching less perfused and deeper tumor areas
  • Indication to overcome drug resistance
  • Induction of immune response by regional hyperthermia

Background

Thermosome’s non-invasive technology is based on proprietary thermosensitive liposomes (TSLs) using a novel, patent-protected phospholipid (DPPG2) loaded with anticancer drugs. These carriers (DPPG2-TSLs) are administered intravenously and safely encapsulate the drug at normal body temperature. Once they reach the heated target area (40-43°C) via the bloodstream, they immediately release the drug into the blood vessels supplying the tumor (intravascular drug release). Due to the drug’s tissue affinity, it enters the tumor and increases local concentrations up to 15-fold compared to conventional systemic application. These high local drug concentrations, which also reach less well perfused areas, significantly improve treatment efficacy and can overcome drug resistance – benefits that cannot be achieved with conventional systemic drug administration due to toxicities.

Unlike other targeted approaches, our DPPG2-TSL technology is not dependent on molecular targets, which often limits the population of eligible patients due to the highly heterogeneous nature and escape mechanisms of many tumors.

Heating is achieved by clinically established, mild regionally focused heating techniques such as microwave or ultrasound devices. This regional mild heating has been shown to activate the immunosuppressive tumor environment.

Relevant Publications

Sebeke L, Gómez JDC, Heijman E, Rademann P, Maul AC, Ekdawi S, Vlachakis S, Toker D, Mink BL, Schubert-Quecke C, Yeo SY, Schmidt P, Lucas C, Brodesser S, Hossann M, Lindner LH, Grüll H.Hyperthermia-induced doxorubicin delivery from thermosensitive liposomes via MR-HIFU in a pig model.J. Control. Release. 2022;343: 798-812.read publication
Hossann M, Hirschberger J, Schmidt R, Baumgartner C, Zimmermann K, Baer S, Ratzlaff C, Peller M, Troedson K, Limmer S, Brühschwein A, Dörfelt R, Kreutzmann N, Wess G, Knösel T, Schagon O, Fischer J, Grüll H, Willerding L, Schmidt M, Meyer-Lindenberg A, Issels RD, Schwaiger M, Eggermont AM, Ten Hagen TL, Lindner LH.A heat-activated drug delivery platform based on phosphatidyl-(oligo)-glycerol nanocarrier for effective cancer treatment.Advanced NanoBiomed Research. 2021;1:2000089.read publication
Brummelhuis ISG, Simons M, Lindner LH, Kort S, de Jong S, Hossann M, Witjes JA, Oosterwijk E.DPPG2-based thermosensitive liposomes as drug delivery system for effective muscle-invasive bladder cancer treatment in vivo.Int. J. Hyperthermia. 2021;38:1415–1424.read publication
Lokerse WJM, Lazarian A, Kleinhempel A, Petrini M, Schwarz P, Hossann M, Holdt LM, Mailänder V, Lindner LH.Mechanistic investigation of thermosensitive liposome immunogenicity and understanding the drivers for circulation half-life: A polyethylene glycol versus 1,2-dipalmitoyl-sn-glycero-3-phosphodiglycerol study.J Control Release. 2021;333:1-15.read publication
van Valenberg FJP, Brummelhuis ISG, Lindner LH, Kuhnle F, Wedmann B, Schweizer P, Hossann M, Witjes JA, Oosterwijk E.DPPG2-based thermosensitive liposomes with encapsulated doxorubicin combined with hyperthermia lead to higher doxorubicin concentrations in the bladder compared to conventional application in pigs: a rationale for the treatment of muscle-invasive bladder cancer.Int J Nanomedicine. 2021:16:75-88.read publication
Mittag JJ, Kneidl B, Preiß T, Hossann M, Winter G, Wuttke S, Engelke H, Rädler JO.Impact of plasma protein binding on cargo release by thermosensitive liposomes probed by fluorescence correlation spectroscopy.Eur J Pharm Biopharm. 2017 Oct;119:215-223.read publication
Manzoor AA, Lindner LH, Landon CD, Park JY, Simnick AJ, Dreher MR, Das S, Hanna G, Park W, Chilkoti A, Koning GA, ten Hagen TL, Needham D, Dewhirst MW.Overcoming limitations in nanoparticle drug delivery: triggered, intravascular release to improve drug penetration into tumors.Cancer Res. 2012 Nov 1;72(21):5566-75.read publication
Hossann M, Syunyaeva Z, Schmidt R, Zengerle A, Eibl H, Issels RD, Lindner LH.Proteins and cholesterol lipid vesicles are mediators of drug release from thermosensitive liposomes.J Control Release. 2012 Sep 10;162(2):400-6.read publication
Lindner LH, Eichhorn ME, Eibl H, Teichert N, Schmitt-Sody M, Issels RD, Dellian M.Novel temperature-sensitive liposomes with prolonged circulation time.Clin Cancer Res. 2004 Mar 15;10(6):2168-78. PubMed PMID: 15041738.read publication