2013 Fiscal Year Final Research Report

Development of combination therapy with hyperthermia and targeted therapy

Research Project

Project/Area Number	24792006
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Pathobiological dentistry/Dental radiology
Research Institution	Yokohama City University
Principal Investigator	NAKASHIMA Hideyuki 横浜市立大学, 附属病院, 助教 (30437032)
Project Period (FY)	2012-04-01 – 2014-03-31
Keywords	温熱療法 / 分子標的薬 / 併用療法 / 口腔癌
Research Abstract	Interleukin-13 receptor alpha 2 chain (IL-13Ra2), a unique tumor-associated antigen, is a promising target for cancer immunotherapy. IL13-PE, a targeted cytotoxin composed of IL-13 and mutated Pseudomonas exotoxin, induces specific killing of IL-13Ra2 positive tumor cells. Our objective is whether hyperthermia treatment of oral squamous cell carcinoma (OSCC) can modulate the expression of IL-13Ra2 and increase their sensitivity to IL13-PE. OSCC cell lines, HSC-3 and SCC-25 cells were heated with 43 degree for 1 hour. The proliferation of heat-stressed OSCC cells showed more than 50% growth inhibition compared to control cells. IL-13Ra2 was up-regulated after heating of OSCC cells. Protein synthesis inhibition assay with IL13-PE showed that heat-stressed OSCC cells decreased the number of IC50 compared to that of without heated OSCC cells. The percentages of apoptotic cells increased in OSCC cells treated with IL13-PE after hyperthermia compared with controls.