HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gautherot, E. Articles by Barbet, J. Search for Related Content PubMed PubMed Citation Articles by Gautherot, E. Articles by Barbet, J.

Pretargeted Radioimmunotherapy of Human Colorectal Xenografts with Bispecific Antibody and ¹³¹I-Labeled Bivalent Hapten

Immunotech SA, Marseille
Laboratoire de Biopathologie Nerveuse et Musculaire, Université de Provence, Faculté de Médecine, Marseille
Laboratoire d'Immunologie Cellulaire, Hôpital Pitié-Salpétrière, Paris, France

Correspondence: For correspondence or reprints contact: Emmanuel Gautherot, PhD, Antibody Department, Immunotech SA, 130 Avenue De Lattre de Tassigny, BP 177 13276, Marseille Cedex 9, France.

ABSTRACT

We have developed a pretargeting strategy, called the affinity enhancement system (AES), which uses bispecific antibodies to target radiolabeled bivalent haptens to tumor cells. The aim of this study was to evaluate the potential of the AES for the radioimmunotherapy (RIT) of LS174T colorectal xenografts in comparison with RIT with directly labeled F(ab')₂ fragment. Methods: A total of 6 groups of tumor-bearing mice were treated using anticarcinoembryonic antigen (CEA) x anti-diethylenetri-amine pentaacetic acid (DTPA)-ln bispecific antibody (BsF(ab')₂) and ¹³¹I-labeled di-DTPA-In bivalent hapten. Three groups of mice were injected with various activities of ¹³¹I-labeled bivalent hapten (75,96, and 112 MBq) 20 h after administration of BsF(ab)'2. Three other groups were injected with an almost constant activity of labeled hapten (102 MBq) at 3 time periods (15,30, and 48 h) after BsF(ab')₂ administration. For conventional RIT, mice were treated with 96 MBq ¹³¹I-labeled anti-CEAF(ab')₂. Control groups were left untreated. Toxicity and tumor growth were monitored at weekly intervals. Results: Doses used for conventional RIT induced severe toxicity and resulted in death of several treated animals. Nevertheless, all surviving animals treated with ¹³¹I-labeled anti-CEA F(ab')₂ relapsed shortly after treatment (tumor growth delay = 48 ± 13 d). For animals treated with the AES reagents, toxicity varied with the pretargeting time interval and the administered activity. For 20-h pretargeting time, the maximum tolerated dose was 96 MBq. For all AES RIT except 1 (with 48-h pretargeting time interval and growth delay of 82 ± 26 d), no tumor growth was observed over a period of 8 mo. Furthermore, based on clinical and histotogic criteria, 33% of the treated mice were considered cured. Conclusion: High cure rates of LS174T colon carcinoma were achieved with the AES, and the flexibility of the pretargeting approach allowed the control of hematologic toxicity, which is the main limitation to dose escalation with conventional RIT.

Key Words: radioimmunotherapy • pretargeting • colorectal carcinoma • bispecific antibody • ¹³¹I

This article has been cited by other articles:

				R. M. Sharkey, H. Karacay, S. Litwin, E. A. Rossi, W. J. McBride, C.-H. Chang, and D. M. Goldenberg Improved Therapeutic Results by Pretargeted Radioimmunotherapy of Non-Hodgkin's Lymphoma with a New Recombinant, Trivalent, Anti-CD20, Bispecific Antibody Cancer Res., July 1, 2008; 68(13): 5282 - 5290. [Abstract] [Full Text] [PDF]

				J. M. Pagel, A. Pantelias, N. Hedin, S. Wilbur, L. Saganic, Y. Lin, D. Axworthy, D. K. Hamlin, D. S. Wilbur, A. K. Gopal, et al. Evaluation of CD20, CD22, and HLA-DR Targeting for Radioimmunotherapy of B-Cell Lymphomas Cancer Res., June 15, 2007; 67(12): 5921 - 5928. [Abstract] [Full Text] [PDF]

				D. Moosmayer, D. Berndorff, C.-H. Chang, R. M. Sharkey, A. Rother, S. Borkowski, E. A. Rossi, W. J. McBride, T. M. Cardillo, D. M. Goldenberg, et al. Bispecific antibody pretargeting of tumor neovasculature for improved systemic radiotherapy of solid tumors. Clin. Cancer Res., September 15, 2006; 12(18): 5587 - 5595. [Abstract] [Full Text] [PDF]

				J. M. Pagel, Y. Lin, N. Hedin, A. Pantelias, D. Axworthy, D. Stone, D. K. Hamlin, D. S. Wilbur, and O. W. Press Comparison of a tetravalent single-chain antibody-streptavidin fusion protein and an antibody-streptavidin chemical conjugate for pretargeted anti-CD20 radioimmunotherapy of B-cell lymphomas Blood, July 1, 2006; 108(1): 328 - 336. [Abstract] [Full Text] [PDF]

				D. M. Goldenberg, R. M. Sharkey, G. Paganelli, J. Barbet, and J.-F. Chatal Antibody Pretargeting Advances Cancer Radioimmunodetection and Radioimmunotherapy J. Clin. Oncol., February 10, 2006; 24(5): 823 - 834. [Abstract] [Full Text] [PDF]

				D. J. Buchsbaum, M.B. Khazaeli, D. B. Axworthy, J. Schultz, T. R. Chaudhuri, K. R. Zinn, M. Carpenter, and A. F. LoBuglio Intraperitoneal Pretarget Radioimmunotherapy with CC49 Fusion Protein Clin. Cancer Res., November 15, 2005; 11(22): 8180 - 8185. [Abstract] [Full Text] [PDF]

				H. Karacay, P.-Y. Brard, R. M. Sharkey, C.-H. Chang, E. A. Rossi, W. J. McBride, D. R. Ragland, I. D. Horak, and D. M. Goldenberg Therapeutic Advantage of Pretargeted Radioimmunotherapy Using a Recombinant Bispecific Antibody in a Human Colon Cancer Xenograft Clin. Cancer Res., November 1, 2005; 11(21): 7879 - 7885. [Abstract] [Full Text] [PDF]

				R. M. Sharkey, H. Karacay, T. M. Cardillo, C.-H. Chang, W. J. McBride, E. A. Rossi, I. D. Horak, and D. M. Goldenberg Improving the Delivery of Radionuclides for Imaging and Therapy of Cancer Using Pretargeting Methods Clin. Cancer Res., October 1, 2005; 11(19): 7109s - 7121s. [Abstract] [Full Text] [PDF]

				S. J. DeNardo, C. M. Richman, H. Albrecht, P. A. Burke, A. Natarajan, A. Yuan, J. P. Gregg, R.T. O'Donnell, and G. L. DeNardo Enhancement of the Therapeutic Index: From Nonmyeloablative and Myeloablative toward Pretargeted Radioimmunotherapy for Metastatic Prostate Cancer Clin. Cancer Res., October 1, 2005; 11(19): 7187s - 7194s. [Abstract] [Full Text] [PDF]

				F. G. van Schaijk, M. Broekema, E. Oosterwijk, J. E.M. van Eerd, B. J. McBride, D. M. Goldenberg, F. H.M. Corstens, and O. C. Boerman Residualizing Iodine Markedly Improved Tumor Targeting Using Bispecific Antibody-Based Pretargeting J. Nucl. Med., June 1, 2005; 46(6): 1016 - 1022. [Abstract] [Full Text] [PDF]

				R. M. Sharkey, G. Hajjar, D. Yeldell, A. Brenner, J. Burton, A. Rubin, and D. M. Goldenberg A Phase I Trial Combining High-Dose 90Y-Labeled Humanized Anti-CEA Monoclonal Antibody with Doxorubicin and Peripheral Blood Stem Cell Rescue in Advanced Medullary Thyroid Cancer J. Nucl. Med., April 1, 2005; 46(4): 620 - 633. [Abstract] [Full Text] [PDF]

				R. M. Sharkey The Direct Route May Not Be the Best Way to Home J. Nucl. Med., March 1, 2005; 46(3): 391 - 394. [Full Text] [PDF]

				R. M. Sharkey and D. M. Goldenberg Perspectives on Cancer Therapy with Radiolabeled Monoclonal Antibodies J. Nucl. Med., January 1, 2005; 46(1_suppl): 115S - 127S. [Abstract] [Full Text] [PDF]

				J. He, G. Liu, S. Gupta, Y. Zhang, M. Rusckowski, and D. J. Hnatowich Amplification Targeting: A Modified Pretargeting Approach with Potential for Signal Amplification--Proof of a Concept J. Nucl. Med., June 1, 2004; 45(6): 1087 - 1095. [Abstract] [Full Text] [PDF]

				E. A. Rossi, R. M. Sharkey, W. McBride, H. Karacay, L. Zeng, H. J. Hansen, D. M. Goldenberg, and C.-H. Chang Development of New Multivalent-bispecific Agents for Pretargeting Tumor Localization and Therapy Clin. Cancer Res., September 1, 2003; 9(10): 3886S - 3896. [Abstract] [Full Text] [PDF]

				R. M. Sharkey, H. Karacay, H. Richel, W. J. McBride, E. A. Rossi, K. Chang, D. Yeldell, G. L. Griffiths, H. J. Hansen, and D. M. Goldenberg Optimizing Bispecific Antibody Pretargeting for Use in Radioimmunotherapy Clin. Cancer Res., September 1, 2003; 9(10): 3897S - 3913. [Abstract] [Full Text] [PDF]

				O. C. Boerman, F. G. van Schaijk, W. J.G. Oyen, and F. H.M. Corstens Pretargeted Radioimmunotherapy of Cancer: Progress Step by Step J. Nucl. Med., March 1, 2003; 44(3): 400 - 411. [Abstract] [Full Text] [PDF]

				D. J. Buchsbaum and A. F. LoBuglio Targeting of 125I-Labeled B Lymphocyte Stimulator J. Nucl. Med., March 1, 2003; 44(3): 434 - 436. [Full Text] [PDF]

				R. M. Sharkey, W. J. McBride, H. Karacay, K. Chang, G. L. Griffiths, H. J. Hansen, and D. M. Goldenberg A Universal Pretargeting System for Cancer Detection and Therapy Using Bispecific Antibody Cancer Res., January 15, 2003; 63(2): 354 - 363. [Abstract] [Full Text] [PDF]

				D. M. Goldenberg Targeted Therapy of Cancer with Radiolabeled Antibodies J. Nucl. Med., May 1, 2002; 43(5): 693 - 713. [Abstract] [Full Text] [PDF]

				C.-H. Chang, R. M. Sharkey, E. A. Rossi, H. Karacay, W. McBride, H. J. Hansen, J.-F. Chatal, J. Barbet, and D. M. Goldenberg Molecular Advances in Pretargeting Radioimunotherapy with Bispecific Antibodies Mol. Cancer Ther., May 1, 2002; 1(7): 553 - 563. [Abstract] [Full Text] [PDF]

				G. Liu, K. Mang'era, N. Liu, S. Gupta, M. Rusckowski, and D. J. Hnatowich Tumor Pretargeting in Mice Using 99mTc-Labeled Morpholino, a DNA Analog J. Nucl. Med., March 1, 2002; 43(3): 384 - 391. [Abstract] [Full Text] [PDF]

				O. W. Press, M. Corcoran, K. Subbiah, D. K. Hamlin, D. S. Wilbur, T. Johnson, L. Theodore, E. Yau, R. Mallett, D. L. Meyer, et al. A comparative evaluation of conventional and pretargeted radioimmunotherapy of CD20-expressing lymphoma xenografts Blood, October 15, 2001; 98(8): 2535 - 2543. [Abstract] [Full Text] [PDF]

				J. F. Gestin, A. Loussouarn, M. Bardies, E. Gautherot, A. Gruaz-Guyon, C. Sai-Maurel, J. Barbet, C. Curtet, J. F. Chatal, and A. Faivre-Chauvet Two-Step Targeting of Xenografted Colon Carcinoma Using a Bispecific Antibody and 188Re-Labeled Bivalent Hapten: Biodistribution and Dosimetry Studies J. Nucl. Med., January 1, 2001; 42(1): 146 - 153. [Abstract] [Full Text] [PDF]

				A. Goel, S. Augustine, J. Baranowska-Kortylewicz, D. Colcher, B. J. M. Booth, G. Pavlinkova, M. Tempero, and S. K. Batra Single-Dose versus Fractionated Radioimmunotherapy of Human Colon Carcinoma Xenografts Using 131I-labeled Multivalent CC49 Single-chain Fvs Clin. Cancer Res., January 1, 2001; 7(1): 175 - 184. [Abstract] [Full Text]