Defucosylated Humanized Anti-CCR4 Monoclonal Antibody KW-0761 as a Novel Immunotherapeutic Agent for Adult T-cell Leukemia/Lymphoma

Ishii, Toshihiko; Ishida, Takashi; Utsunomiya, Atae; Inagaki, Atsushi; Yano, Hiroki; Komatsu, Hirokazu; Iida, Shinsuke; Imada, Kazunori; Uchiyama, Takashi; Akinaga, Shiro; Shitara, Kenya; Ueda, Ryuzo

doi:10.1158/1078-0432.ccr-09-2697

Cited by 221 publications

(183 citation statements)

References 47 publications

Supporting

Mentioning

174

Contrasting

Unclassified

Order By: Relevance

“…We have shown that a therapeutic anti-CCR4 mAb does deplete Treg cells in vitro (39,40) and in vivo in humanized mice (27). Furthermore, we confirmed the CD25 + CD4 + FOXP3 + Treg depletion activity mediated by the humanized anti-CCR4 mAb mogamulizumab (KW-0761) in humans (41)(42)(43)(44). Therefore, a combination of Tax-CTL adoptive immunotherapy with mogamulizumab to act not only as an anti-ATL agent but also to deplete Treg cells would be promising.…”

Section: Discussionsupporting

confidence: 60%

Autologous Tax-Specific CTL Therapy in a Primary Adult T Cell Leukemia/Lymphoma Cell–Bearing NOD/Shi-scid, IL-2Rγnull Mouse Model

Awata

Ishida

Suzuki

et al. 2013

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

We expanded human T-lymphotropic virus type 1 Tax-specific CTL in vitro from PBMC of three individual adult T cell leukemia/lymphoma (ATL) patients and assessed their therapeutic potential in an in vivo model using NOG mice bearing primary ATL cells from the respective three patients (ATL/NOG). In these mice established with cells from a chronic-type patient, treatment by i.p. injection of autologous Tax-CTL resulted in greater infiltration of CD8-positive T cells into each ATL lesion. This was associated with a significant decrease of ATL cell infiltration into blood, spleen, and liver. Tax-CTL treatment also significantly decreased human soluble IL-2R concentrations in the sera. In another group of ATL/NOG mice, Tax-CTL treatment led to a significant prolongation of survival time. These findings show that Tax-CTL can infiltrate the tumor site, recognize, and kill autologous ATL cells in mice in vivo. In ATL/NOG mice with cells from an acute-type patient, whose postchemotherapeutic remission continued for >18 mo, antitumor efficacy of adoptive Tax-CTL therapy was also observed. However, in ATL/NOG mice from a different acute-type patient, whose ATL relapsed after 6 mo of remission, no efficacy was observed. Thus, although the therapeutic effects were different for different ATL patients, to the best of our knowledge, this is the first report that adoptive therapy with Ag-specific CTL expanded from a cancer patient confers antitumor effects, leading to significant survival benefit for autologous primary cancer cell–bearing mice in vivo. The present study contributes to research on adoptive CTL therapy, which should be applicable to several types of cancer.

show abstract

Section: Discussionsupporting

confidence: 60%

Autologous Tax-Specific CTL Therapy in a Primary Adult T Cell Leukemia/Lymphoma Cell–Bearing NOD/Shi-scid, IL-2Rγnull Mouse Model

Awata

Ishida

Suzuki

et al. 2013

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“… 136 Potent anti-tumor effect of KM2760 in NOG mice bearing adult T cell leukemia/lymphoma (ATLL) cellsIto et al 137 Mogamulizumab/ POTELIGEO/ KM0761CC chemokine receptor 4 (CCR4)afucosylatedFUT8 −/− CHO cells (Potelligent® Technology)Induced potent tumor growth inhibition and enhanced survival in ATLL tumor-bearing mice over vehicle controlIshii et al. 138 Humanized IgG1 Benralizumab /MEDI-563Humanized IgG1IL-5RαafucosylatedFUT8 −/− CHO cells (Potelligent® Technology)Efficient eosinophils depletion in non-human primatesKolbeck et al. 123 KHK2823 Humanized IgG1IL-3Rα (CD123)afucosylatedFUT8 −/− CHO cells (Potelligent® Technology)Tumor growth inhibition of human AML cell line MOLM-13 grafted into nude rats compared to vehicle control(e) Significant depletion of IL-3Rα-positive cells in the peripheral blood of cynomolgus monkeys Low fucose Elotuzumab/ HuLuc63-LFSignaling Lymphocyte Activation Molecule (SLAMF7, also called CS1)ReducedYB2/0 cellsEnhanced anti-tumor activity in OPM2 xenograft SCID mice modelHsi et al.…”

Section: Enhanced Adcc Activities By Afucosylated Antibodies In In VImentioning

confidence: 99%

The “less-is-more” in therapeutic antibodies: Afucosylated anti-cancer antibodies with enhanced antibody-dependent cellular cytotoxicity

Pereira

Chan

Lin

et al. 2018

mAbs

267

211

View full text Add to dashboard Cite

Therapeutic monoclonal antibodies are the fastest growing class of biological therapeutics for the treatment of various cancers and inflammatory disorders. In cancer immunotherapy, some IgG1 antibodies rely on the Fc-mediated immune effector function, antibody-dependent cellular cytotoxicity (ADCC), as the major mode of action to deplete tumor cells. It is well-known that this effector function is modulated by the N-linked glycosylation in the Fc region of the antibody. In particular, absence of core fucose on the Fc N-glycan has been shown to increase IgG1 Fc binding affinity to the FcγRIIIa present on immune effector cells such as natural killer cells and lead to enhanced ADCC activity. As such, various strategies have focused on producing afucosylated antibodies to improve therapeutic efficacy. This review discusses the relevance of antibody core fucosylation to ADCC, different strategies to produce afucosylated antibodies, and an update of afucosylated antibody drugs currently undergoing clinical trials as well as those that have been approved.

show abstract

“…GA101 (obinutuzumab) is a GE, type II anti-CD20 mAb that has recently been approved by the U.S. Food and Drug Administration for the first line treatment of patients with chronic lymphocytic leukemia (CLL) in combination with chlorambucil (18)(19)(20). In Japan, the GE CCR4 Ab mogamulizumab has been approved for treatment of patients with relapsed or refractory CCR4 + T cell leukemia-lymphoma (21).…”

mentioning

confidence: 99%

Glycoengineering of Therapeutic Antibodies Enhances Monocyte/Macrophage-Mediated Phagocytosis and Cytotoxicity

Herter

Birk

Klein

et al. 2014

The Journal of Immunology

134

100

View full text Add to dashboard Cite

Therapeutic Abs possess several clinically relevant mechanisms of action including perturbation of tumor cell signaling, activation of complement-dependent cytotoxicity, Ab-dependent cellular cytotoxicity (ADCC), Ab-dependent cellular phagocytosis (ADCP), and induction of adaptive immunity. In view of the important role of phagocytic lineage cells in the mechanism of action of therapeutic Abs, we analyzed FcγR receptor-dependent effector functions of monocytes and macrophages triggered by glycoengineered (GE) Abs (having enhanced FcγRIIIa [CD16a] binding affinity) versus their wild-type (WT) counterparts under different experimental conditions. We first defined the precise FcγR repertoire on classical and nonclassical intermediate monocytes—M1 and M2c macrophage populations. We further show that WT and GE Abs display comparable binding and induce similar effector functions (ADCC and ADCP) in the absence of nonspecific, endogenous IgGs. However, in the presence of these IgGs (i.e., in a situation that more closely mimics physiologic conditions), GE Abs display significantly superior binding and promote stronger monocyte and macrophage activity. These data show that in addition to enhancing CD16a-dependent NK cell cytotoxicity, glycoengineering also enhances monocyte and macrophage phagocytic and cytotoxic activities through enhanced binding to CD16a under conditions that more closely resemble the physiologic setting.

show abstract

Defucosylated Humanized Anti-CCR4 Monoclonal Antibody KW-0761 as a Novel Immunotherapeutic Agent for Adult T-cell Leukemia/Lymphoma

Cited by 221 publications

References 47 publications

Autologous Tax-Specific CTL Therapy in a Primary Adult T Cell Leukemia/Lymphoma Cell–Bearing NOD/Shi-scid, IL-2Rγnull Mouse Model

Autologous Tax-Specific CTL Therapy in a Primary Adult T Cell Leukemia/Lymphoma Cell–Bearing NOD/Shi-scid, IL-2Rγnull Mouse Model

The “less-is-more” in therapeutic antibodies: Afucosylated anti-cancer antibodies with enhanced antibody-dependent cellular cytotoxicity

Glycoengineering of Therapeutic Antibodies Enhances Monocyte/Macrophage-Mediated Phagocytosis and Cytotoxicity

Contact Info

Product

Resources

About