Jeremy Steinbacher - A Multifunctional Mesothelin Antibody-tagged Microparticle Targets Human Mesotheliomas

Version 1

      Publication Details (including relevant citation   information): Macura, Sherrill L., Hillegass, Jedd M.,   Steinbacher, Jeremy L., MacPherson, Maximilian B., Shukla, Arti,   Beuschel, Stacie L., Perkins, Timothy N., Butnor, Kelly J.,   Lathrop, Melissa J., Sayan, Mutlay, Hekmatyar, Khan, Taatjes,   Douglas J., Kauppinen, Risto A., Landry, Christopher C., Mossman,   Brooke T., Journal of Histochemistry & Cytochemistry  , 2012, 60 (9 ), pp 658 -674

      Abstract: Pleural and peritoneal mesotheliomas   (MMs) are chemoresistant tumors with no effective therapeutic   strategies. The authors first injected multifunctional,   acid-prepared mesoporous spheres (APMS), microparticles   functionalized with tetraethylene glycol oligomers,   intraperitoneally into rodents. Biodistribution of APMS was   observed in major organs, peritoneal lavage fluid (PLF), and   urine of normal mice and rats. After verification of increased   mesothelin in human mesotheliomas injected into severe combined   immunodeficient (SCID) mice, APMS were then functionalized with   an antibody to mesothelin (APMS-MB) or bovine serum albumin   (BSA), a nonspecific protein control, and tumor targeting was   evaluated by inductively coupled plasma mass spectrometry and   multifluorescence confocal microscopy. Some APMS were initially   cleared via the urine over a 24 hr period, and small amounts were   observed in liver, spleen, and kidneys at 24 hr and 6 days.   Targeting with APMS-MB increased APMS uptake in mesenteric tumors   at 6 days. Approximately 10% to 12% of the initially injected   amount was observed in both spheroid and mesenteric MM at this   time point. The data suggest that localized delivery of APMS-MB   into the peritoneal cavity after encapsulation of drugs, DNA, or   macromolecules is a novel therapeutic approach for MM and other   tumors (ovarian and pancreatic) that overexpress mesothelin.

      Address (URL):