SNM Annual Meeting Abstracts
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     



J Nucl Med. 2008; 49 (Supplement 1):313P
This Article
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Sharkey, R.
Right arrow Articles by Goldenberg, D.
PubMed
Right arrow Articles by Sharkey, R.
Right arrow Articles by Goldenberg, D.

Oncology-Basic Science: Basic Science

Basic Science Posters

Pretargeted radioimmunotherapy of pancreatic cancer with a recombinant tri-Fab bispecific antibody and a 90Y-hapten-peptide

Robert Sharkey1, Habibe Karacay1, Edmund Rossi2, Chein-Hsing Chang2, William McBride3 and David Goldenberg1

1 Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, New Jersey; 2 IBC Pharmaceuticals, Inc., Morris Plains, New Jersey; 3 Immunomedics, Inc., Morris Plains, New Jersey

1331

Objectives: Pretargeting is a promising procedure for improving radioimmunotherapy with less hematologic toxicity. We evaluated conditions to optimize pretargeted therapy with 90Y-DOTA-di-HSG peptide (IMP-288) and TF10, a humanized recombinant bispecific antibody with 2 Fabs that bind a pancreatic cancer mucin antigen identified by the antibody PAM4, and 1 Fab binding to the hapten HSG (histamine-succinyl-glycine).

Methods: Biodistribution and therapy studies using TF10 and radiolabeled IMP-288 were performed in nude mice bearing s.c. CaPan1 human pancreatic tumors. For therapy, TF10-pretargeted 90Y-IMP-288 was given alone or fractionated in combination with gemcitabine (human equivalent of 900 mg/m2 weekly x 3; repeated 3 times over 11 weeks).

Results: Optimal pretargeting required 10-20x molar excess of TF10 than IMP-288 given 16 h apart. 111In-IMP-288 tumor uptake was 15-25% ID/g within 1 h of injection, achieving tumor/blood, kidneys, and liver ratios >1000:1, 7:1, and >50:1, respectively. TF-10 pretargeted 90Y-IMP-288, 9.25 and 18.5 MBq, arrested the growth of established tumors, curing 3/10 and 7/10 animals, respectively, without appreciable hematologic toxicity. Three cycles of 9.25 MBq of TF10-pretargeted 90Y-IMP-288 given every 4 weeks in combination with the standard gemcitabine treatment regimen improved responses compared to pretargeted peptide alone, extending median survival from 4.9 weeks to 18.2 weeks (P = 0.004).

Conclusions: TF10-pretargeted therapy is a promising treatment for pancreatic cancer with minimal hematologic toxicity. Combination with gemcitabine further improves the response.

Research Support: In part, NCI grant CA115755.





This Article
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Sharkey, R.
Right arrow Articles by Goldenberg, D.
PubMed
Right arrow Articles by Sharkey, R.
Right arrow Articles by Goldenberg, D.