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 Hellström, I. Articles by Hellström, K. E. Search for Related Content PubMed PubMed Citation Articles by Hellström, I. Articles by Hellström, K. E.

Highly Tumor-reactive, Internalizing, Mouse Monoclonal Antibodies to Le^y-related Cell Surface Antigens¹

ONCOGEN, Seattle, Washington 98121

Two monoclonal antibodies, designated BR64 (IgG1) and BR96 (IgG3), were generated that, according to immunohistology, bind selectively to carcinomas of the colon, breast, ovary, and lung. They have no or very low reactivity with normal human tissues, except for the fact that BR64 stains capillaries in the hearts from certain normal donors and that both monoclonal antibodies stain some epithelial cells from the gastrointestinal system, including stomach. Preliminary studies indicate that at least a portion of the epitope recognized by BR64 and BR96 is a Le^y carbohydrate chain. Both monoclonal antibodies can be "ipternalized" by antigen-positive tumor cells, since immunoconjugates with ricin A-chain are cytotoxic. BR96 has the additional properties of being cytotoxic by itself, and it can mediate antibody-dependent cellular cytotoxicity and complement dependent cytotoxicity.

¹ Supported by ONCOGEN.

² To whom requests for reprints should be addressed, at ONCOGEN, 3005 First Avenue, Seattle, WA 98121.

Received 8/ 1/89. Revised 11/13/89.

This article has been cited by other articles:

				L. H. SCHMIDT, S. BIESTERFELD, A. KUMMEL, A. FALDUM, M. SEBASTIAN, C. TAUBE, R. BUHL, and R. WIEWRODT Tissue Microarrays are Reliable Tools for the Clinicopathological Characterization of Lung Cancer Tissue Anticancer Res, January 1, 2009; 29(1): 201 - 209. [Abstract] [Full Text] [PDF]

				L. Martensson, R. Nilsson, T. Ohlsson, H.-O. Sjogren, S.-E. Strand, and J. Tennvall Improved Tumor Targeting and Decreased Normal Tissue Accumulation through Extracorporeal Affinity Adsorption in a Two-Step Pretargeting Strategy Clin. Cancer Res., September 15, 2007; 13(18): 5572s - 5576s. [Abstract] [Full Text] [PDF]

				A. M. Scott, N. Tebbutt, F.-T. Lee, T. Cavicchiolo, Z. Liu, S. Gill, A. M.T. Poon, W. Hopkins, F. E. Smyth, C. Murone, et al. A Phase I Biodistribution and Pharmacokinetic Trial of Humanized Monoclonal Antibody Hu3s193 in Patients with Advanced Epithelial Cancers that Express the Lewis-Y Antigen Clin. Cancer Res., June 1, 2007; 13(11): 3286 - 3292. [Abstract] [Full Text] [PDF]

				D. Loo, N. Pryer, P. Young, T. Liang, S. Coberly, K. L. King, K. Kang, P. Roberts, M. Tsao, X. Xu, et al. The glycotope-specific RAV12 monoclonal antibody induces oncosis in vitro and has antitumor activity against gastrointestinal adenocarcinoma tumor xenografts in vivo Mol. Cancer Ther., March 1, 2007; 6(3): 856 - 865. [Abstract] [Full Text] [PDF]

				L. Martensson, R. Nilsson, T. Ohlsson, H.-O. Sjogren, S.-E. Strand, and J. Tennvall Reduced Myelotoxicity with Sustained Tumor Concentration of Radioimmunoconjugates in Rats after Extracorporeal Depletion J. Nucl. Med., February 1, 2007; 48(2): 269 - 276. [Abstract] [Full Text] [PDF]

				H. Farhan, C. Schuster, M. Klinger, E. Weisz, G. Waxenecker, M. Schuster, V. Sexl, G. C. Mudde, M. Freissmuth, and R. Kircheis Inhibition of Xenograft Tumor Growth and Down-Regulation of ErbB Receptors by an Antibody Directed against Lewis Y Antigen J. Pharmacol. Exp. Ther., December 1, 2006; 319(3): 1459 - 1466. [Abstract] [Full Text] [PDF]

				R. M. Sharkey and D. M. Goldenberg Targeted Therapy of Cancer: New Prospects for Antibodies and Immunoconjugates CA Cancer J Clin, July 1, 2006; 56(4): 226 - 243. [Abstract] [Full Text] [PDF]

				P. A. McCarron, S. A. Olwill, W. M.Y. Marouf, R. J. Buick, B. Walker, and C. J. Scott Antibody Conjugates and Therapeutic Strategies Mol. Interv., December 1, 2005; 5(6): 368 - 380. [Abstract] [Full Text] [PDF]

				F. T. Lee, A. J. Mountain, M. P. Kelly, C. Hall, A. Rigopoulos, T. G. Johns, F. E. Smyth, M. W. Brechbiel, E. C. Nice, A. W. Burgess, et al. Enhanced Efficacy of Radioimmunotherapy with 90Y-CHX-A''-DTPA-hu3S193 by Inhibition of Epidermal Growth Factor Receptor (EGFR) Signaling with EGFR Tyrosine Kinase Inhibitor AG1478 Clin. Cancer Res., October 1, 2005; 11(19): 7080s - 7086s. [Abstract] [Full Text] [PDF]

				L. Martensson, Z. Wang, R. Nilsson, T. Ohlsson, P. Senter, H.-O. Sjogren, S.-E. Strand, and J. Tennvall Determining Maximal Tolerable Dose of the Monoclonal Antibody BR96 Labeled with 90Y or 177Lu in Rats: Establishment of a Syngeneic Tumor Model to Evaluate Means to Improve Radioimmunotherapy Clin. Cancer Res., October 1, 2005; 11(19): 7104s - 7108s. [Abstract] [Full Text] [PDF]

				M. Schuster, P. Umana, C. Ferrara, P. Brunker, C. Gerdes, G. Waxenecker, S. Wiederkum, C. Schwager, H. Loibner, G. Himmler, et al. Improved Effector Functions of a Therapeutic Monoclonal Lewis Y-Specific Antibody by Glycoform Engineering Cancer Res., September 1, 2005; 65(17): 7934 - 7941. [Abstract] [Full Text] [PDF]

				G. Ragupathi, N. X. Liu, C. Musselli, S. Powell, K. Lloyd, and P. O. Livingston Antibodies against Tumor Cell Glycolipids and Proteins, but Not Mucins, Mediate Complement-Dependent Cytotoxicity J. Immunol., May 1, 2005; 174(9): 5706 - 5712. [Abstract] [Full Text] [PDF]

				C. J. Henry, M. S. Buss, I. Hellstrom, K. E. Hellstrom, W. G. Brewer, J. N. Bryan, and C. B. Siegall Clinical Evaluation of BR96 sFv-PE40 Immunotoxin Therapy in Canine Models of Spontaneously Occurring Invasive Carcinoma Clin. Cancer Res., January 15, 2005; 11(2): 751 - 755. [Abstract] [Full Text] [PDF]

				P. Carter, L. Smith, and M. Ryan Identification and validation of cell surface antigens for antibody targeting in oncology Endocr. Relat. Cancer, December 1, 2004; 11(4): 659 - 687. [Abstract] [Full Text] [PDF]

				W. C. Rose and R. Wild Therapeutic Synergy of Oral Taxane BMS-275183 and Cetuximab versus Human Tumor Xenografts Clin. Cancer Res., November 1, 2004; 10(21): 7413 - 7417. [Abstract] [Full Text] [PDF]

				E. R. Boghaert, L. Sridharan, D. C. Armellino, K. M. Khandke, J. F. DiJoseph, A. Kunz, M. M. Dougher, F. Jiang, L. B. Kalyandrug, P. R. Hamann, et al. Antibody-Targeted Chemotherapy with the Calicheamicin Conjugate hu3S193-N-Acetyl {gamma} Calicheamicin Dimethyl Hydrazide Targets Lewisy and Eliminates Lewisy-Positive Human Carcinoma Cells and Xenografts Clin. Cancer Res., July 1, 2004; 10(13): 4538 - 4549. [Abstract] [Full Text] [PDF]

				M. Klinger, H. Farhan, H. Just, H. Drobny, G. Himmler, H. Loibner, G. C. Mudde, M. Freissmuth, and V. Sexl Antibodies Directed against Lewis-Y Antigen Inhibit Signaling of Lewis-Y Modified ErbB Receptors Cancer Res., February 1, 2004; 64(3): 1087 - 1093. [Abstract] [Full Text] [PDF]

				G. Ragupathi, D. M. Coltart, L. J. Williams, F. Koide, E. Kagan, J. Allen, C. Harris, P. W. Glunz, P. O. Livingston, and S. J. Danishefsky On the power of chemical synthesis: Immunological evaluation of models for multiantigenic carbohydrate-based cancer vaccines PNAS, October 15, 2002; 99(21): 13699 - 13704. [Abstract] [Full Text] [PDF]

				J. A. Posey, M. B. Khazaeli, M. A. Bookman, A. Nowrouzi, W. E. Grizzle, J. Thornton, D. E. Carey, J. M. Lorenz, A. P. Sing, C. B. Siegall, et al. A Phase I Trial of the Single-Chain Immunotoxin SGN-10 (BR96 sFv-PE40) in Patients with Advanced Solid Tumors Clin. Cancer Res., October 1, 2002; 8(10): 3092 - 3099. [Abstract] [Full Text] [PDF]

				V. Kudryashov, P. W. Glunz, L. J. Williams, S. Hintermann, S. J. Danishefsky, and K. O. Lloyd Toward optimized carbohydrate-based anticancer vaccines: Epitope clustering, carrier structure, and adjuvant all influence antibody responses to Lewisy conjugates in mice PNAS, March 13, 2001; 98(6): 3264 - 3269. [Abstract] [Full Text] [PDF]

				D. R. Siemens, B. D. Elzey, D. M. Lubaroff, C. Bohlken, R. J. Jensen, A. K. Swanson, and T. L. Ratliff Cutting Edge: Restoration of the Ability to Generate CTL in Mice Immune to Adenovirus by Delivery of Virus in a Collagen-Based Matrix J. Immunol., January 15, 2001; 166(2): 731 - 735. [Abstract] [Full Text] [PDF]

				J. Chen, Z. Cheng, T. J. Hoffman, S. S. Jurisson, and T. P. Quinn Melanoma-targeting Properties of 99mTechnetium-labeled Cyclic {{alpha}}-Melanocyte-stimulating Hormone Peptide Analogues Cancer Res., October 1, 2000; 60(20): 5649 - 5658. [Abstract] [Full Text]

				K. Clarke, F.-T. Lee, M. W. Brechbiel, F. E. Smyth, L. J. Old, and A. M. Scott In Vivo Biodistribution of a Humanized Anti-Lewis Y Monoclonal Antibody (hu3S193) in MCF-7 Xenografted BALB/c Nude Mice Cancer Res., September 1, 2000; 60(17): 4804 - 4811. [Abstract] [Full Text]

				K. Clarke, F.-T. Lee, M. W. Brechbiel, F. E. Smyth, L. J. Old, and A. M. Scott Therapeutic Efficacy of Anti-Lewisy Humanized 3S193 Radioimmunotherapy in a Breast Cancer Model: Enhanced Activity When Combined with Taxol Chemotherapy Clin. Cancer Res., September 1, 2000; 6(9): 3621 - 3628. [Abstract] [Full Text]

				M. N. Saleh, S. Sugarman, J. Murray, J. B. Ostroff, D. Healey, D. Jones, C. R. Daniel, D. LeBherz, H. Brewer, N. Onetto, et al. Phase I Trial of the Anti-Lewis Y Drug Immunoconjugate BR96-Doxorubicin in Patients With Lewis Y-Expressing Epithelial Tumors J. Clin. Oncol., June 11, 2000; 18(11): 2282 - 2292. [Abstract] [Full Text] [PDF]

				A. M. Scott, D. Geleick, M. Rubira, K. Clarke, E. C. Nice, F. E. Smyth, E. Stockert, E. C. Richards, F. J. Carr, W. J. Harris, et al. Construction, Production, and Characterization of Humanized Anti-Lewis Y Monoclonal Antibody 3S193 for Targeted Immunotherapy of Solid Tumors Cancer Res., June 1, 2000; 60(12): 3254 - 3261. [Abstract] [Full Text]

				S. Muller-Loennies, C.R. MacKenzie, S. I. Patenaude, S. V. Evans, P. Kosma, H. Brade, L. Brade, and S. Narang Characterization of high affinity monoclonal antibodies specific for chlamydial lipopolysaccharide Glycobiology, February 1, 2000; 10(2): 121 - 130. [Abstract] [Full Text] [PDF]

				A. W. Tolcher, S. Sugarman, K. A. Gelmon, R. Cohen, M. Saleh, C. Isaacs, L. Young, D. Healey, N. Onetto, and W. Slichenmyer Randomized Phase II Study of BR96-Doxorubicin Conjugate in Patients With Metastatic Breast Cancer J. Clin. Oncol., February 1, 1999; 17(2): 478 - 478. [Abstract] [Full Text] [PDF]

				H.G. Haggerty, W.A. Warner, C.R. Comereski, W.M. Peden, L.E. Mezza, B.D. Damle, C.B. Siegall, and T.J. Davidson BR96 sFv-PE40 Immunotoxin: Nonclinical Safety Assessment Toxicol Pathol, January 1, 1999; 27(1): 87 - 94. [Abstract] [PDF]

				M. J. Rosok, M. Eghtedarzadeh-Kondri, K. Young, J. Bajorath, S. Glaser, and D. Yelton Analysis of BR96 Binding Sites for Antigen and Anti-Idiotype by Codon-Based Scanning Mutagenesis J. Immunol., March 1, 1998; 160(5): 2353 - 2359. [Abstract] [Full Text] [PDF]

				M. J. Rosok, D. E. Yelton, L. J. Harris, J. Bajorath, K.-E. Hellstrom, I. Hellstrom, G. A. Cruz, K. Kristensson, H. Lin, W. D. Huse, et al. A Combinatorial Library Strategy for the Rapid Humanization of Anticarcinoma BR96 Fab J. Biol. Chem., September 13, 1996; 271(37): 22611 - 22618. [Abstract] [Full Text] [PDF]

				C. Hatem, N. Gough, and D. Fambrough Multiple mRNAs encode the avian lysosomal membrane protein LAMP-2, resulting in alternative transmembrane and cytoplasmic domains J. Cell Sci., January 5, 1995; 108(5): 2093 - 2100. [Abstract] [PDF]

				C. R. Comereski, W. M. Peden, T. J. Davidson, G. L. Warner, R. S. Hirth, and J. D. Frantz BR96-Doxorubicin Conjugate (BMS-182248) Versus Doxorubicin: A Comparative Toxicity Assessment in Rats Toxicol Pathol, September 1, 1994; 22(5): 473 - 488. [Abstract] [PDF]

				P. Trail, D Willner, S. Lasch, A. Henderson, S Hofstead, A. Casazza, R. Firestone, I Hellstrom, and K. Hellstrom Cure of xenografted human carcinomas by BR96-doxorubicin immunoconjugates Science, July 9, 1993; 261(5118): 212 - 215. [Abstract] [PDF]