| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
1 Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Tokyo, Japan; 2 Department of Molecular Preventive Medicine, School of Medicine, The University of Tokyo, Tokyo, Japan; 3 Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Science, Nagoya, Japan; and 4 BioWa, Inc., Princeton, New Jersey
Human IgG1 antibodies with low fucose contents in their asparagine-linked oligosaccharides have been shown recently to exhibit potent antibody-dependent cellular cytotoxicity (ADCC) in vitro. To additionally investigate the efficacy of the human IgG1 with enhanced ADCC, we generated the defucosylated chimeric anti-CC chemokine receptor 4 (CCR4) IgG1 antibody KM2760. KM2760 exhibited much higher ADCC using human peripheral blood mononuclear cells (PBMCs) as effector cells compared with the highly fucosylated, but otherwise identical IgG1, KM3060. In addition, KM2760 also exhibited potent ADCC in the presence of lower concentrations of human PBMCs than KM3060. Because CCR4 is a selective marker of T-cell leukemia/lymphoma, the effectiveness of KM2760 for T-cell malignancy was evaluated in several mouse models. First, to compare the antitumor activity of KM2760 and KM3060, we constructed a human PBMC-engrafted mouse model to determine ADCC efficacy with human effector cells. In this model, KM2760 showed significantly higher antitumor efficacy than KM3060, indicating that KM2760 retains its high potency in vivo. Second, KM2760 suppressed tumor growth in both syngeneic and xenograft mouse models in which human PBMCs were not engrafted. Although murine effector cells exhibited marginal ADCC mediated by KM2760 and KM3060, KM2760 unexpectedly showed higher efficacy than KM3060 in a syngeneic mouse model, suggesting that KM2760 functions in murine effector system in vivo via an unknown mechanism that differs from that in human. These results indicate that defucosylated antibodies with enhanced ADCC as well as potent antitumor activity in vivo are promising candidates for the novel antibody-based therapy.
This article has been cited by other articles:
|
|
 |
|
  A. Ito, T. Ishida, A. Utsunomiya, F. Sato, F. Mori, H. Yano, A. Inagaki, S. Suzuki, H. Takino, M. Ri, et al. Defucosylated Anti-CCR4 Monoclonal Antibody Exerts Potent ADCC against Primary ATLL Cells Mediated by Autologous Human Immune Cells in NOD/Shi-scid, IL-2R{gamma}null Mice In Vivo J. Immunol., October 1, 2009; 183(7): 4782 - 4791. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Cardarelli, M.-C. Moldovan-Loomis, B. Preston, A. Black, D. Passmore, T.-H. Chen, S. Chen, J. Liu, M. R. Kuhne, M. Srinivasan, et al. In vitro and In vivo Characterization of MDX-1401 for Therapy of Malignant Lymphoma Clin. Cancer Res., May 15, 2009; 15(10): 3376 - 3383. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Bruhns, B. Iannascoli, P. England, D. A. Mancardi, N. Fernandez, S. Jorieux, and M. Daeron Specificity and affinity of human Fc{gamma} receptors and their polymorphic variants for human IgG subclasses Blood, April 16, 2009; 113(16): 3716 - 3725. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Shibata-Koyama, S. Iida, A. Okazaki, K. Mori, K. Kitajima-Miyama, S. Saitou, S. Kakita, Y. Kanda, K. Shitara, K. Kato, et al. The N-linked oligosaccharide at Fc{gamma}RIIIa Asn-45: an inhibitory element for high Fc{gamma}RIIIa binding affinity to IgG glycoforms lacking core fucosylation Glycobiology, February 1, 2009; 19(2): 126 - 134. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Picchio, E. Scala, D. Pomponi, E. Caprini, M. Frontani, I. Angelucci, A. Mangoni, C. Lazzeri, M. Perez, D. Remotti, et al. CXCL13 Is Highly Produced by Sezary Cells and Enhances Their Migratory Ability via a Synergistic Mechanism Involving CCL19 and CCL21 Chemokines Cancer Res., September 1, 2008; 68(17): 7137 - 7146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Natsume, M. In, H. Takamura, T. Nakagawa, Y. Shimizu, K. Kitajima, M. Wakitani, S. Ohta, M. Satoh, K. Shitara, et al. Engineered Antibodies of IgG1/IgG3 Mixed Isotype with Enhanced Cytotoxic Activities Cancer Res., May 15, 2008; 68(10): 3863 - 3872. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yano, T. Ishida, A. Inagaki, T. Ishii, J. Ding, S. Kusumoto, H. Komatsu, S. Iida, H. Inagaki, and R. Ueda Defucosylated Anti CC Chemokine Receptor 4 Monoclonal Antibody Combined with Immunomodulatory Cytokines: A Novel Immunotherapy for Aggressive/Refractory Mycosis Fungoides and Sezary Syndrome Clin. Cancer Res., November 1, 2007; 13(21): 6494 - 6500. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Strome, E. A. Sausville, and D. Mann A Mechanistic Perspective of Monoclonal Antibodies in Cancer Therapy Beyond Target-Related Effects Oncologist, September 1, 2007; 12(9): 1084 - 1095. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Baatar, P. Olkhanud, D. Newton, K. Sumitomo, and A. Biragyn CCR4-Expressing T Cell Tumors Can Be Specifically Controlled via Delivery of Toxins to Chemokine Receptors J. Immunol., August 1, 2007; 179(3): 1996 - 2004. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Suzuki, R. Niwa, S. Saji, M. Muta, M. Hirose, S. Iida, Y. Shiotsu, M. Satoh, K. Shitara, M. Kondo, et al. A Nonfucosylated Anti-HER2 Antibody Augments Antibody-Dependent Cellular Cytotoxicity in Breast Cancer Patients Clin. Cancer Res., March 15, 2007; 13(6): 1875 - 1882. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Kanda, T. Yamada, K. Mori, A. Okazaki, M. Inoue, K. Kitajima-Miyama, R. Kuni-Kamochi, R. Nakano, K. Yano, S. Kakita, et al. Comparison of biological activity among nonfucosylated therapeutic IgG1 antibodies with three different N-linked Fc oligosaccharides: the high-mannose, hybrid, and complex types Glycobiology, January 1, 2007; 17(1): 104 - 118. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Shoji-Hosaka, Y. Kobayashi, M. Wakitani, K. Uchida, R. Niwa, K. Nakamura, and K. Shitara Enhanced Fc-Dependent Cellular Cytotoxicity of Fc Fusion Proteins Derived from TNF Receptor II and LFA-3 by Fucose Removal from Asn-Linked Oligosaccharides J. Biochem., December 1, 2006; 140(6): 777 - 783. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Natsume, M. Wakitani, N. Yamane-Ohnuki, E. Shoji-Hosaka, R. Niwa, K. Uchida, M. Satoh, and K. Shitara Fucose Removal from Complex-Type Oligosaccharide Enhances the Antibody-Dependent Cellular Cytotoxicity of Single-Gene-Encoded Bispecific Antibody Comprising of Two Single-Chain Antibodies Linked to the Antibody Constant Region J. Biochem., September 1, 2006; 140(3): 359 - 368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ishida, T. Ishii, A. Inagaki, H. Yano, H. Komatsu, S. Iida, H. Inagaki, and R. Ueda Specific Recruitment of CC Chemokine Receptor 4-Positive Regulatory T Cells in Hodgkin Lymphoma Fosters Immune Privilege Cancer Res., June 1, 2006; 66(11): 5716 - 5722. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Alfonso-Perez, S. Lopez-Giral, N. E. Quintana, J. Loscertales, P. Martin-Jimenez, and C. Munoz Anti-CCR7 monoclonal antibodies as a novel tool for the treatment of chronic lymphocyte leukemia J. Leukoc. Biol., June 1, 2006; 79(6): 1157 - 1165. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Iida, H. Misaka, M. Inoue, M. Shibata, R. Nakano, N. Yamane-Ohnuki, M. Wakitani, K. Yano, K. Shitara, and M. Satoh Nonfucosylated Therapeutic IgG1 Antibody Can Evade the Inhibitory Effect of Serum Immunoglobulin G on Antibody-Dependent Cellular Cytotoxicity through its High Binding to Fc{gamma}RIIIa. Clin. Cancer Res., May 1, 2006; 12(9): 2879 - 2887. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Sturla, F. Fruscione, K. Noda, E. Miyoshi, N. Taniguchi, P. Contini, and M. Tonetti Core fucosylation of N-linked glycans in leukocyte adhesion deficiency/congenital disorder of glycosylation IIc fibroblasts Glycobiology, October 1, 2005; 15(10): 924 - 934. [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]
|
|
|
|
 |
|
 P. Carter and C. F. McDonagh Designer Antibody-Based Therapeutics for Oncology Am. Assoc. Cancer Res. Educ. Book, April 1, 2005; 2005(1): 147 - 154. [Full Text] [PDF]
|
|
|
|
|
|
R. Niwa, M. Sakurada, Y. Kobayashi, A. Uehara, K. Matsushima, R. Ueda, K. Nakamura, and K. Shitara Enhanced Natural Killer Cell Binding and Activation by Low-Fucose IgG1 Antibody Results in Potent Antibody-Dependent Cellular Cytotoxicity Induction at Lower Antigen Density Clin. Cancer Res., March 15, 2005; 11(6): 2327 - 2336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Savage Aggressive Peripheral T-Cell Lymphomas (Specified and Unspecified Types) Hematology, January 1, 2005; 2005(1): 267 - 277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ishida, S. Iida, Y. Akatsuka, T. Ishii, M. Miyazaki, H. Komatsu, H. Inagaki, N. Okada, T. Fujita, K. Shitara, et al. The CC Chemokine Receptor 4 as a Novel Specific Molecular Target for Immunotherapy in Adult T-Cell Leukemia/Lymphoma Clin. Cancer Res., November 15, 2004; 10(22): 7529 - 7539. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Niwa, S. Hatanaka, E. Shoji-Hosaka, M. Sakurada, Y. Kobayashi, A. Uehara, H. Yokoi, K. Nakamura, and K. Shitara Enhancement of the Antibody-Dependent Cellular Cytotoxicity of Low-Fucose IgG1 Is Independent of Fc{gamma}RIIIa Functional Polymorphism Clin. Cancer Res., September 15, 2004; 10(18): 6248 - 6255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ishida, H. Inagaki, A. Utsunomiya, Y. Takatsuka, H. Komatsu, S. Iida, G. Takeuchi, T. Eimoto, S. Nakamura, and R. Ueda CXC Chemokine Receptor 3 and CC Chemokine Receptor 4 Expression in T-Cell and NK-Cell Lymphomas with Special Reference to Clinicopathological Significance for Peripheral T-Cell Lymphoma, Unspecified Clin. Cancer Res., August 15, 2004; 10(16): 5494 - 5500. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Olszewski and M. L. Grossbard Empowering Targeted Therapy: Lessons from Rituximab Sci. Signal., July 13, 2004; 2004(241): pe30 - pe30. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
