Abstract 3517: Use of a novel synthetic biomaterial to induce mild whole body hyperthermia for the treatment of cancer in a preclinical model

Abstract

Abstract Hyperthermia is currently being investigated as an alternative form or cancer therapy. Numerous basic and pre-clinical published reports have shown the antitumor effects of hyperthermia in various cancer models. High temperatures, low duration (heat shock) will have a direct killing effect on exposed cells. The limitation to this approach is the restriction of tumor location and associated side effects. Low temperature, high duration whole body hyperthermia (WBH) is generally considered to be the least toxic but requires long exposures that are generally uncomfortable or inconvenient to the patients. In the present study, we show the efficacy of a synthetic far-infrared emitting biomaterial to induce and evaluate its therapeutic potential when used alone or in combination with chemotherapy. We used BioRubber (BR, Yamamoto Bio-Technology Inc., Anaheim, CA), a state of the art biomaterial that emits far infrared radiation in the 4-25 μm spectral ranges. To determine the efficacy to induce mild whole body hyperthermia, athymic nude mice were house in BR lined cages. Core body temperatures of mice housed in BR-lined cages were significantly higher than mice housed in unlined cages and were maintained up to 2 weeks during continuous exposure (37.70oC vs. 36.75oC, p=0.038, respectively.). To determine the antitumor effects of WBH, KU7/GFP-bearing nude mice were housed in cages lined with BR for 28 days. Non-significant tumor growth inhibition was observed in tumors of mice housed in BR. Histological and immunohistochemical analysis revealed increased granulocyte activity in tumors of BR-exposed mice. Additionally, increased levels of C-GSF, GM-CSF, TNFα and IL-12p70 corresponded to exposure to WBH. To determine the long term safety and efficacy of mild WBH and chemotherapy in deep tumors, we carried out a survival study using immunodeficient mice orthotopically inoculated with KU7/GFP cells and treated doxorubicin (Dox) alone or in combination with BR. Although no treatment efficacy was observed in mice treated with BR with regards to tumor size (tumor size according to the expression of GFP was 350.5, 309.7, 357.4, 257.3 for control, WBH, Dox and WBH/Dox groups, respectively), survival was improved for mice exposed to BR. Survival rates were 50% (5/10), 70% (7/10), 10% (1/10) and 50% (5/10), for control, WBH, Dox and WBH/Dox groups, respectively. It is unclear if mild WBH has a direct antitumor effect; however, it appears that BR-induced mild WBH may be capable of inducing immuno-stimulatory that may improve survival in a preclinical model. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3517. doi:1538-7445.AM2012-3517