Cetuximab delivery and antitumor effects are enhanced by mild hyperthermia in a xenograft mouse model of pancreatic cancer

Cancer Science
Ryoichi MiyamotoNobuhiro Ohkohchi

Abstract

Even with current promising antitumor antibodies, their antitumor effects on stroma-rich solid cancers have been insufficient. We used mild hyperthermia with the intent of improving drug delivery by breaking the stromal barrier. Here, we provide preclinical evidence of cetuximab + mild hyperthermia therapy. We used four in vivo pancreatic cancer xenograft mouse models with different stroma amounts (scarce, MIAPaCa-2; moderate, BxPC-3; and abundant, Capan-1 and Ope-xeno). Cetuximab (1 mg/kg) was given systemically, and the mouse leg tumors were concurrently heated using a water bath method for 30 min at three different temperatures, 25°C (control), 37°C (intra-abdominal organ level), or 41°C (mild hyperthermia) (n = 4, each group). The evaluated variables were the antitumor effects, represented by tumor volume, and in vivo cetuximab accumulation, indirectly quantified by the immunohistochemical fluorescence intensity value/cell using antibodies against human IgG Fc. At 25°C, the antitumor effects were sufficient, with a cetuximab accumulation value (florescence intensity/cell) of 1632, in the MIAPaCa-2 model, moderate (1063) in the BxPC-3 model, and negative in the Capan-1 and Ope-xeno models (760, 461). By applying 37°C or 41°C...Continue Reading

References

Jun 25, 1992·The New England Journal of Medicine·D S Zimmon, R Ferstenberg
Feb 13, 1992·The New England Journal of Medicine·A L Warshaw, C Fernández-del Castillo
Jan 1, 1988·Recent Results in Cancer Research. Fortschritte Der Krebsforschung. Progrès Dans Les Recherches Sur Le Cancer·O Dahl
May 14, 1999·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·M UranoY Nishimura
Mar 22, 2001·Radiation Research·C W SongR J Griffin
Aug 16, 2002·Annals of Oncology : Official Journal of the European Society for Medical Oncology·J van der Zee
Jun 23, 2004·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Derek AtkinsStephan Störkel
Sep 20, 2005·Biochimica Et Biophysica Acta·Therese Deramaudt, Anil K Rustgi
Dec 13, 2005·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·C W SongR Griffin
Jul 25, 2006·Nature Reviews. Cancer·Andrew I Minchinton, Ian F Tannock
Sep 16, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Rolf D Issels
Jun 13, 2009·Science·Peter Olson, Douglas Hanahan
Jul 8, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Philip A PhilipCharles D Blanke
Jan 6, 2011·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Ruud P M DingsRobert J Griffin
Feb 8, 2011·CA: a Cancer Journal for Clinicians·Ahmedin JemalDavid Forman
Sep 15, 2012·Cancer Cell·Christine M ArditoJens T Siveke
Feb 9, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Li LiGerben A Koning
Oct 23, 2014·The New England Journal of Medicine·Fotios LoupakisAlfredo Falcone

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Citations

Sep 13, 2017·Expert Opinion on Drug Delivery·Carlos Daniel MartinsWim J G Oyen
Aug 31, 2018·Interactive Cardiovascular and Thoracic Surgery·Hyun-Sung LeeBryan M Burt
Oct 9, 2020·Scientific Reports·Yu Tang, Yanguang Cao

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