Pretargeted radioimmunotherapy of pancreatic cancer xenografts: TF10-90Y-IMP-288 alone and combined with gemcitabine

Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
H KaracayD M Goldenberg

Abstract

Pancreatic cancer is a silent disease that most commonly presents in an already metastatic form. Current treatment options provide little survival benefit. Radiolabeled PAM4 IgG, a monoclonal antibody that recognizes a unique epitope associated with a mucin found almost exclusively in pancreatic cancer, has shown encouraging therapeutic effects in animal models and in early clinical testing ((90)Y-humanized PAM4 IgG, (90)Y-clivatuzumab tetraxetan). The studies reported herein examine a new pretargeting procedure for delivering therapeutic radionuclides. We prepared a humanized, recombinant tri-Fab bispecific monoclonal antibody (bsmAb) (TF10) using specificity for targeting pancreatic cancer of PAM4 and another Fab binding to a hapten (histamine-succinyl-glycine [HSG]) and tested this in a pretargeting setting with a (90)Y-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-di-HSG-peptide (pretargeted radioimmunotherapy [PT-RAIT]). Nude mice bearing established Capan-1 human pancreatic cancer xenografts were given TF10 and then received the (90)Y peptide as a single bolus dose 19 h later, or the therapy cycle was fractionated weekly. Other studies examined different combinations with gemcitabine. PT-RAIT of 18.5 MBq (...Continue Reading

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Mar 8, 2012·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Robert M SharkeyDavid M Goldenberg
Oct 12, 2011·Bioconjugate Chemistry·Guozheng LiuDonald J Hnatowich
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Jan 29, 2011·Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al]·Birgit MellerJohannes Meller
Feb 22, 2016·Seminars in Nuclear Medicine·Susan Evans-AxelssonJörgen Elgqvist
Jun 2, 2012·Expert Opinion on Biological Therapy·David M Goldenberg, Robert M Sharkey
Jun 29, 2012·Trends in Pharmacological Sciences·Edmund A RossiChien-Hsing Chang
Jul 27, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Federica ZorattoS Tomao
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Apr 16, 2015·Frontiers in Pharmacology·Françoise Kraeber-BodéréJacques Barbet
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Sep 7, 2012·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Robert M SharkeyDavid M Goldenberg
Nov 6, 2010·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Rafke SchoffelenOtto C Boerman
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