Skip to main content
SpringerLink
Log in

Progress in Clinical Use of CC Chemokine Receptor 4 Antibody for Regulatory T Cell Suppression

  • Chapter
Inflammation and Immunity in Cancer

Abstract

Recent clinical research advances in tumor immunity provide hope for the development of a novel tumor immunotherapy. Many clinical studies of cancer vaccines over the past 10 years have shown the augmentation of tumor immunity in some patients, although the clinical effects have been low. In addition, it was reported that blocking regulatory molecules involved in the immune checkpoint is important for immune activation in both in vitro and in vivo studies. In particular, studies using blocking antibodies to cytotoxic T lymphocyte-associated antigen (CTLA)-4, programmed cell death protein (PD)-1, or PD-1 ligand 1 (PD-L1) observed significant clinical effects including complete remission, suggesting that regulation of regulatory signals in the immune checkpoint is a new direction for the development of new drugs based on tumor immunity. As regulatory T cells (Tregs) also plays a key role in immune regulation, just as the regulatory molecules in the immune checkpoint become targets for the development of novel tumor immunotherapy, they may also become a target for development. Several reports have suggested that Tregs that infiltrate tumor sites as well as regulatory signals for immune checkpoints can inhibit tumor immunity, which is one explanation why treatment by cancer vaccine is limited. CC chemokine receptor 4 (CCR4) is selectively expressed on effector Tregs, and humanized monoclonal antibodies to CCR4 have been developed as a drug, ‘mogamulizumab’, to treat adult T cell leukemia/lymphoma (ATLL). Mogamulizumab depletes both ATLL cells and normal Tregs, resulting in the recovery of immune function in ATLL patients. Mogamulizumab is now expected to be accepted for use as a novel immuno-activator for tumor therapy by depletion of Tregs and is undergoing phase Ia/Ib studies for treatment of solid tumors in the lung, esophagus, intestine, ovary, and melanoma.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Baghdadi M, Nagao H, Yoshiyama H, Akiba H, Yagita H, Dosaka-Akita H, Jinushi M (2013) Combined blockade of TIM-3 and TIM-4 augments cancer vaccine efficacy against established melanomas. Cancer Immunol Immunother 62(4):629–637

    Article  CAS  PubMed  Google Scholar 

  • Baixeras E, Huard B, Miossec C, Jitsukawa S, Martin M, Hercend T, Auffray C, Triebel F, Piatier-Tonneau D (1992) Characterization of the lymphocyte activation gene 3-encoded protein. A new ligand for human leukocyte antigen class II antigens. J Exp Med 176(2):327–337

    Article  CAS  PubMed  Google Scholar 

  • Barber DL et al (2006) Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 439:682–687

    Article  CAS  PubMed  Google Scholar 

  • Bennett CL, Christie J, Ramsdell F, Brunkow ME, Ferguson PJ, Whitesell L, Kelly TE, Saulsbury FT, Chance PF, Ochs HD (2001) The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet 27(1):20–21

    Article  CAS  PubMed  Google Scholar 

  • Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366(26):2455–2465

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cedeno-Laurent F, Dimitroff CJ (2012) Galectins and their ligands: negative regulators of anti-tumor immunity. Glycoconj J 29(8–9):619–625

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Coiffier B, Lepage E, Briere J et al (2002) CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 346:235–242

    Article  CAS  PubMed  Google Scholar 

  • Cunningham D et al (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351:337–345

    Article  CAS  PubMed  Google Scholar 

  • Curiel TJ, Wei S, Dong H, Alvarez X, Cheng P, Mottram P, Krzysiek R, Knutson KL, Daniel B, Zimmermann MC, David O, Burow M, Gordon A, Dhurandhar N, Myers L, Berggren R, Hemminki A, Alvarez RD, Emilie D, Curiel DT, Chen L, Zou W (2003) Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med 9(5):562–567

    Article  CAS  PubMed  Google Scholar 

  • Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, Zhu Y, Wei S, Kryczek I, Daniel B, Gordon A, Myers L, Lackner A, Disis ML, Knutson KL, Chen L, Zou W (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10(9):942–949

    Article  CAS  PubMed  Google Scholar 

  • Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, Lennon VA, Celis E, Chen L, Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, Lennon VA, Celis E, Chen L (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 8(8):793–800

    CAS  PubMed  Google Scholar 

  • Duvic M, Pinter-Brown L, Foss FM, Sokol L, Jorgensen J, Spitalny GL, Kim YH (2010) Results of a phase 1/2 study for KW-0761, a monoclonal antibody directed against CC chemokine receptor type 4 (CCR4), in CTCL patients. Blood (ASH Annual Meeting Abstracts) 116:962

    Google Scholar 

  • Egen JG, Allison JP (2002) Cytotoxic T lymphocyte antigen-4 accumulation in the immunological synapse is regulated by TCR signal strength. Immunity 16(1):23–35

    Article  CAS  PubMed  Google Scholar 

  • Fontenot JD, Gavin MA, Rudensky AY (2003) Foxp3 programs the development and function of CD4 + CD25+ regulatory T cells. Nat Immunol 4(4):330–336

    Article  CAS  PubMed  Google Scholar 

  • Fourcade J, Sun Z, Pagliano O, Guillaume P, Luescher IF, Sander C, Kirkwood JM, Olive D, Kuchroo V, Zarour HM (2012) CD8(+) T cells specific for tumor antigens can be rendered dysfunctional by the tumor microenvironment through upregulation of the inhibitory receptors BTLA and PD-1. Cancer Res 72(4):887–896

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Francisco LM, Salinas VH, Brown KE, Vanguri VK, Freeman GJ, Kuchroo VK, Sharpe AH (2009) PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med 206(13):3015–3029

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC, Horton HF, Fouser L, Carter L, Ling V, Bowman MR, Carreno BM, Collins M, Wood CR, Honjo T (2000) Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192(7):1027–1034

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gavin MA, Rasmussen JP, Fontenot JD, Vasta V, Manganiello VC, Beavo JA, Rudensky AY (2007) Foxp3-dependent programme of regulatory T-cell differentiation. Nature 445(7129):771–775

    Article  CAS  PubMed  Google Scholar 

  • Grosso JF, Kelleher CC, Harris TJ, Maris CH, Hipkiss EL, De Marzo A, Anders R, Netto G, Getnet D, Bruno TC, Goldberg MV, Pardoll DM, Drake CG (2007) LAG-3 regulates CD8+ T cell accumulation and effector function in murine self- and tumor-tolerance systems. J Clin Invest 117(11):3383–3392

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, Wolchok JD, Hersey P, Joseph RW, Weber JS, Dronca R, Gangadhar TC, Patnaik A, Zarour H, Joshua AM, Gergich K, Elassaiss-Schaap J, Algazi A, Mateus C, Boasberg P, Tumeh PC, Chmielowski B, Ebbinghaus SW, Li XN, Kang SP, Ribas A (2013) Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. [Epub ahead of print]

    Google Scholar 

  • Hill JA, Feuerer M, Tash K, Haxhinasto S, Perez J, Melamed R, Mathis D, Benoist C (2007) Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature. Immunity 27(5):786–800

    Article  CAS  PubMed  Google Scholar 

  • Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbé C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363(8):711–723

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hori S, Nomura T, Sakaguchi S (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299(5609):1057–1061

    Article  CAS  PubMed  Google Scholar 

  • Huang CT, Workman CJ, Flies D, Pan X, Marson AL, Zhou G, Hipkiss EL, Ravi S, Kowalski J, Levitsky HI, Powell JD, Pardoll DM, Drake CG, Vignali DA (2004) Role of LAG-3 in regulatory T cells. Immunity 21(4):503–513

    Article  CAS  PubMed  Google Scholar 

  • Ishida T, Ueda R (2006) CCR4 as a novel molecular target for immunotherapy of cancer. Cancer Sci 97(11):1139–1146

    Article  CAS  PubMed  Google Scholar 

  • Ishida T, Ueda R (2011) Immunopathogenesis of lymphoma: focus on CCR4. Cancer Sci 102(1):44–50

    Article  CAS  PubMed  Google Scholar 

  • Ishida Y, Agata Y, Shibahara K, Honjo T (1992) Induced expression of PD‑1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J 11:3887–3895

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ishida T, Utsunomiya A, Iida S, Inagaki H, Takatsuka Y, Kusumoto S, Takeuchi G, Shimizu S, Ito M, Komatsu H, Wakita A, Eimoto T, Matsushima K, Ueda R (2003) Clinical significance of CCR4 expression in adult T-cell leukemia/lymphoma: its close association with skin involvement and unfavorable outcome. Clin Cancer Res 9(10 Pt 1):3625–3634

    CAS  PubMed  Google Scholar 

  • Ishida T, Ishii T, Inagaki A, Yano H, Komatsu H, Iida S, Inagaki H, Ueda R (2006) Specific recruitment of CC chemokine receptor 4-positive regulatory T cells in Hodgkin lymphoma fosters immune privilege. Cancer Res 66(11):5716–5722

    Article  CAS  PubMed  Google Scholar 

  • Ishida T, Joh T, Uike N, Yamamoto K, Utsunomiya A, Yoshida S, Saburi Y, Miyamoto T, Takemoto S, Suzushima H, Tsukasaki K, Nosaka K, Fujiwara H, Ishitsuka K, Inagaki H, Ogura M, Akinaga S, Tomonaga M, Tobinai K, Ueda R (2012) Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T-cell leukemia-lymphoma: a multicenter phase II study. J Clin Oncol 30(8):837–842

    Article  CAS  PubMed  Google Scholar 

  • Ishida T, Ito A, Sato F, Kusumoto S, Iida S, Inagaki H, Morita A, Akinaga S, Ueda R (2013) Stevens-Johnson syndrome associated with mogamulizumab treatment of adult T-cell leukemia/lymphoma. Cancer Sci 104:647–650

    Article  CAS  PubMed  Google Scholar 

  • Ishii T, Ishida T, Utsunomiya A, Inagaki A, Yano H, Komatsu H, Iida S, Imada K, Uchiyama T, Akinaga S, Shitara K, Ueda R (2010) Defucosylated humanized anti-CCR4 monoclonal antibody KW-0761 as a novel immunotherapeutic agent for adult T-cell leukemia/lymphoma. Clin Cancer Res 16(5):1520–3169

    Article  CAS  PubMed  Google Scholar 

  • Konishi J, Yamazaki K, Azuma M, Kinoshita I, Dosaka-Akita H, Nishimura M (2004) B7-H1 expression on non-small cell lung cancer cells and its relationship with tumor-infiltrating lymphocytes and their PD-1 expression. Clin Cancer Res 10(15):5094–5100

    Article  CAS  PubMed  Google Scholar 

  • Kuang DM, Zhao Q, Peng C, Xu J, Zhang JP, Wu C, Zheng L (2009) Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1. J Exp Med 206(6):1327–1337

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Küppers R (2009) The biology of Hodgkin’s lymphoma. Nat Rev Cancer 9(1):15–27

    Article  PubMed  Google Scholar 

  • Lenschow DJ, Walunas TL, Bluestone JA (1996) CD28/B7 system of T cell costimulation. Annu Rev Immunol 14:233–258

    Article  CAS  PubMed  Google Scholar 

  • Linsley PS, Greene JL, Brady W, Bajorath J, Ledbetter JA, Peach R (1994) Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors. Immunity 1(9):793–801

    Article  CAS  PubMed  Google Scholar 

  • Masaki A, Ishida T, Suzuki S, Ito A, Mori F, Sato F, Narita T, Yamada T, Ri M, Kusumoto S, Komatsu H, Tanaka Y, Niimi A, Inagaki H, Iida S, Ueda R (2013) Autologous Tax-specific CTL therapy in a primary adult T cell leukemia/lymphoma cell-bearing NOD/Shi-scid, IL-2Rγnull mouse model. J Immunol 191(1):135–144

    Article  CAS  PubMed  Google Scholar 

  • Matsuda A, Matsuda T, Shibata A, Katanoda K, Sobue T, Nishimoto H, The Japan Cancer Surveillance Research Group (2013) Cancer incidence and incidence rates in Japan in 2007: a study of 21 population-based cancer registries for the Monitoring of Cancer Incidence in Japan (MCIJ) project. Jpn J Clin Oncol 43(3):328–336

    Article  PubMed  Google Scholar 

  • Miyara M, Yoshioka Y, Kitoh A, Shima T, Wing K, Niwa A, Parizot C, Taflin C, Heike T, Valeyre D, Mathian A, Nakahata T, Yamaguchi T, Nomura T, Ono M, Amoura Z, Gorochov G, Sakaguchi S (2009) Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity 30(6):899–911

    Article  CAS  PubMed  Google Scholar 

  • Ngiow SF, Teng MW, Smyth MJ (2011a) Prospects for TIM3-targeted antitumor immunotherapy. Cancer Res 71(21):6567–6571

    Article  CAS  PubMed  Google Scholar 

  • Ngiow SF, von Scheidt B, Akiba H, Yagita H, Teng MW, Smyth MJ (2011b) Anti-TIM3 antibody promotes T cell IFN-γ-mediated antitumor immunity and suppresses established tumors. Cancer Res 71(10):3540–3551

    Article  CAS  PubMed  Google Scholar 

  • Niwa R, Shoji-Hosaka E, Sakurada M, Shinkawa T, Uchida K, Nakamura K, Matsushima K, Ueda R, Hanai N, Shitara K (2004) Defucosylated chimeric anti-CC chemokine receptor 4 IgG1 with enhanced antibody-dependent cellular cytotoxicity shows potent therapeutic activity to T-cell leukemia and lymphoma. Cancer Res 64(6):2127–2133

    Article  CAS  PubMed  Google Scholar 

  • Ohmura Y, Yoshikawa K, Saga S, Ueda R, Kazaoka Y, Yamada S (2008) Combinations of tumor-specific CD8+ CTLs and anti-CD25 mAb provide improved immunotherapy. Oncol Rep 19(5):1265–1270

    CAS  PubMed  Google Scholar 

  • Onizuka S, Tawara I, Shimizu J, Sakaguchi S, Fujita T, Nakayama E (1999) Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor alpha) monoclonal antibody. Cancer Res 59(13):3128–3133

    CAS  PubMed  Google Scholar 

  • Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12(4):252–264

    Article  CAS  PubMed  Google Scholar 

  • Pfreundschuh M, Trumper L, Osterborg A et al (2006) CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol 7:379–391

    Article  CAS  PubMed  Google Scholar 

  • Ribas A (2010) Clinical development of the anti-CTLA-4 antibody tremelimumab. Semin Oncol 37(5):450–454

    Article  CAS  PubMed  Google Scholar 

  • Robert N, Leyland-Jones B, Asmar L, Belt R, Ilegbodu D, Loesch D, Raju R, Valentine E, Sayre R, Cobleigh M, Albain K, McCullough C, Fuchs L, Slamon D (2006) Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer. J Clin Oncol 24(18):2786–2792

    Article  CAS  PubMed  Google Scholar 

  • Robert C, Thomas L, Bondarenko I, O’Day S, JW MD, Garbe C, Lebbe C, Baurain JF, Testori A, Grob JJ, Davidson N, Richards J, Maio M, Hauschild A, Miller WH Jr, Gascon P, Lotem M, Harmankaya K, Ibrahim R, Francis S, Chen TT, Humphrey R, Hoos A, Wolchok JD (2011) Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 364(26):2517–2526

    Article  CAS  PubMed  Google Scholar 

  • Rudd CE, Taylor A, Schneider H (2009) CD28 and CTLA-4 coreceptor expression and signal transduction. Immunol Rev 229(1):12–26

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Schwartz RH (1992) Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell 71(7):1065–1068

    Article  CAS  PubMed  Google Scholar 

  • Shinkawa T, Nakamura K, Yamane N, Shoji-Hosaka E, Kanda Y, Sakurada M, Uchida K, Anazawa H, Satoh M, Yamasaki M, Hanai N, Shitara K (2003) The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgG1 complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity. J Biol Chem 278(5):3466–3473

    Article  CAS  PubMed  Google Scholar 

  • Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344(11):783–792, Phase III clinical trial important for the approval of trastuzumab in combination with chemotherapy as a treatment for HER2 overexpressing metastatic breast cancer

    Article  CAS  PubMed  Google Scholar 

  • Suzuki S, Masaki A, Ishida T, Ito A, Mori F, Sato F, Narita T, Ri M, Kusumoto S, Komatsu H, Fukumori Y, Nishikawa H, Tanaka Y, Niimi A, Inagaki H, Iida S, Ueda R (2012) Tax is a potential molecular target for immunotherapy of adult T-cell leukemia/lymphoma. Cancer Sci 103(10):1764–1773

    Article  CAS  PubMed  Google Scholar 

  • Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366(26):2443–2454

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Van Cutsem E et al (2009) Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360:1408–1417

    Article  PubMed  Google Scholar 

  • van den Berg A, Visser L, Poppema S (1999) High expression of the CC chemokine TARC in Reed-Sternberg cells. A possible explanation for the characteristic T-cell infiltratein Hodgkin’s lymphoma. Am J Pathol 154((6):1685–1691

    Article  PubMed Central  PubMed  Google Scholar 

  • Vignali DA, Collison LW, Workman CJ (2008) How regulatory T cells work. Nat Rev Immunol 8(7):523–532

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Weber J (2010) Immune checkpoint proteins: a new therapeutic paradigm for cance–reclinical background: CTLA-4 and PD-1 blockade. Semin Oncol 37(5):430–439

    Article  CAS  PubMed  Google Scholar 

  • Weihrauch MR, Manzke O, Beyer M, Haverkamp H, Diehl V, Bohlen H, Wolf J, Schultze JL (2005) Elevated serum levels of CC thymus and activation-related chemokine (TARC) in primary Hodgkin’s disease: potential for a prognostic factor. Cancer Res 65(13):5516–5519

    Article  CAS  PubMed  Google Scholar 

  • Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, Segal NH, Ariyan CE, Gordon RA, Reed K, Burke MM, Caldwell A, Kronenberg SA, Agunwamba BU, Zhang X, Lowy I, Inzunza HD, Feely W, Horak CE, Hong Q, Korman AJ, Wigginton JM, Gupta A, Sznol M (2013) Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 369(2):122–133

    Article  CAS  PubMed  Google Scholar 

  • Xiao N, Jorgensen JL, Meghali G, Pramoda C, Decker WK, Kim YH, Madeleine D (2011) Effects of anti-CCR4 antibody (KW-0761) on regulatory T cells and natural killer cells in patients with cutaneous T-cell lymphoma. Blood (ASH Annual Meeting Abstracts) 118:444

    Google Scholar 

  • Yamamoto K, Utsunomiya A, Tobinai K, Tsukasaki K, Uike N, Uozumi K, Yamaguchi K, Yamada Y, Hanada S, Tamura K, Nakamura S, Inagaki H, Ohshima K, Kiyoi H, Ishida T, Matsushima K, Akinaga S, Ogura M, Tomonaga M, Ueda R (2010) Phase I study of KW-0761, a defucosylated humanized anti-CCR4 antibody, in relapsed patients with adult T-cell leukemia-lymphoma and peripheral T-cell lymphoma. J Clin Oncol 28(9):1591–1598

    Article  CAS  PubMed  Google Scholar 

  • Yano H, Ishida T, Inagaki A, Ishii T, Kusumoto S, Komatsu H, Iida S, Utsunomiya A, Ueda R (2007) Regulatory T-cell function of adult T-cell leukemia/lymphoma cells. Int J Cancer 120(9):2052–2057

    Article  CAS  PubMed  Google Scholar 

  • Zarek PE, Huang CT, Lutz ER, Kowalski J, Horton MR, Linden J, Drake CG, Powell JD (2008) A2A receptor signaling promotes peripheral tolerance by inducing T-cell anergy and the generation of adaptive regulatory T cells. Blood 111(1):251–259

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zou W (2006) Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol 6(4):295–307

    Article  CAS  PubMed  Google Scholar 

  • Zou W, Chen L (2008) Inhibitory B7‑family molecules in the tumour microenvironment. Nat Rev Immunol 8:467–477

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Tumor Immunology, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi, Japan

    Susumu Suzuki & Ryuzo Ueda

  2. Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan

    Takashi Ishida

  3. Division of Advanced Research Promotion Institute of Comprehensive Medical Research, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi, Japan

    Kazuhiro Yoshikawa

Authors
  1. Susumu Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takashi Ishida
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kazuhiro Yoshikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ryuzo Ueda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ryuzo Ueda .

Editor information

Editors and Affiliations

  1. Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan

    Tsukasa Seya

  2. Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan

    Misako Matsumoto

  3. Kochi Medical School, Kochi University, Nankoku, Kochi, Japan

    Keiko Udaka

  4. School of Medicine, Sapporo Medical University, Sapporo, Hokkaido, Japan

    Noriyuki Sato

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Japan

About this chapter

Cite this chapter

Suzuki, S., Ishida, T., Yoshikawa, K., Ueda, R. (2015). Progress in Clinical Use of CC Chemokine Receptor 4 Antibody for Regulatory T Cell Suppression. In: Seya, T., Matsumoto, M., Udaka, K., Sato, N. (eds) Inflammation and Immunity in Cancer. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55327-4_17

Download citation

Publish with us

Policies and ethics

Search

Navigation