Development of immuno-stimulatory antibody therapy against cancer

2012 Fiscal Year Final Research Report

• Project/Area Number: 22240089
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor immunology
• Research Institution: Juntendo University
• Principal Investigator: YAGITA Hideo 順天堂大学, 医学部, 先任准教授 (30182306)
• Project Period (FY): 2010 – 2012
• Keywords: がん / 免疫 / 抗体療法 / キラーT細胞 / 4-1BB / CD27 / CTLA-4 / PD-1 / TIM-3

Research Abstract

We have developed novel strategies to induce immunogenic cell death of cancer cells. We have also developed novel strategies to augment anti-tumor immunity by using antibodies activating the immunostimulatory pathways (such as 4-1BB, CD27, and Notch2) and those blocking the immunosuppressive pathways (such as CTLA-4, PD-1, TIM-3) in combination with standard chemotherapy, radiotherapy, and antibody therapy targeting cancer cells.

Research Products

• [Journal Article] Simultaneous blockade of programmed death 1 and vascular endothelial growth factor receptor 2 (VEGFR2) induces synergistic anti-tumor effect in vivo (2013)
  • Author(s): Yasuda S, Sho M, Yamato I, Yoshiji H, Wakatsuki K, Nishiwada S, Yagita H, Nakajima Y
  • Journal Title: Clin Exp Immunol Volume: 172 Pages: 500-506
  • DOI: DOI:10.1111/cei.12069
  • Peer Reviewed
• [Journal Article] Host immunity contributes to the anti-melanoma activity of BRAF inhibitors (2013)
  • Author(s): Knight DA, Ngiow SF, Li M, Parmenter T, Mok S, Cass A, Haynes NM, Kinross K, Yagita H, Koya RC, Greber TG, Ribas A, McArthur GA, Smyth MJ
  • Journal Title: J Cin Inves Volume: 123 Pages: 1371-1381
  • DOI: DOI:10.1172/JCI66236
  • Peer Reviewed
• [Journal Article] Combined blockade of TIM-3 and TIM-4 augments cancer vaccine efficacy against established melanomas (2013)
  • Author(s): Baghdadi M, Nagao H, Yoshiyama H, Akiba H, Yagita H, Dosaka-Akita H, Jinushi M
  • Journal Title: Cancer Immunol Immunother Volume: 62 Pages: 629-637
  • DOI: DOI:10.1007/s00262-012-1371-9
  • Peer Reviewed
• [Journal Article] The TWEAK receptor Fn14 is a therapeutic target in melanoma: Immunotoxins targeting Fn14 receptor for malignant melanoma treatment (2013)
  • Author(s): Zhou H, Ekmekcioglu S, Marks JW, Mohamedali KA, Asrani K, Phillips KK, Brown SA, Cheng E, Weiss MB,Hittelman WN, Tran NL, Yagita H, Winkles JA, Rosenblum MG
  • Journal Title: J Invest Dermatol Volume: 133 Pages: 1052-1062
  • DOI: DOI:10.1038/jid.2-12.402
  • Peer Reviewed
• [Journal Article] Durable adoptive immunotherapy for leukemia produced by manipulation of multiple regulatory pathways of CD8+ T cell tolerance (2013)
  • Author(s): Berrien-Elliott MM, Jackson SR, Meyer JM, Rouskey CJ, Nguyen TL, Yagita H, Greenberg P, Dipaolo RJ, Teague RM
  • Journal Title: Cancer Res Volume: 73 Pages: 605-616
  • DOI: DOI:10.1158/0008-5472.CAN-12-2179
  • Peer Reviewed
• [Journal Article] PD-1 blockade enhances T cell migration to tumors by elevating IFN-γ inducible chemokines (2012)
  • Author(s): Peng W, Liu C, Xu C, Lou Y, Chen J, Yang Y, Yagita H, Overwijk WW, Lizee G, Radvanyi L, Hwu P
  • Journal Title: Cancer Res Volume: 72 Pages: 5209-5218
  • DOI: DOI:10.1158/0008-5472.CAN-12-2179
  • Peer Reviewed
• [Journal Article] Polyfunctional CD4+ T cells are essential for eradicating advanced B-cell lymphoma after chemotherapy (2012)
  • Author(s): Ding ZC, Huang L, Blazar BR, Yagita H, Mellor AL, Munn DH, Zhou G
  • Journal Title: Blood Volume: 120 Pages: 2229-2239
  • DOI: DOI:10.1182/blood-2011-12-398321
  • Peer Reviewed
• [Journal Article] Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1 (2012)
  • Author(s): Chiba S, Baghdadi M, Akiba H, Yoshiyama H, Kinoshita I, Dosaka-Akita H, Fujioka Y, Ohba Y, Gorman JV, Colganb JD, Hirashima M, Uede T, Takaoka A, Yagita H, Jinushi M
  • Journal Title: Nat Immunol Volume: 13 Pages: 832-842
  • DOI: DOI:10.1038/ni.2376
  • Peer Reviewed
• [Journal Article] The CD4+ T-cell help signal is transmitted from APC to CD8+ T-cells via CD27-CD70 interactions (2012)
  • Author(s): Feau S, Garcia Z, Arens R, Yagita H, Borst J, Schoenberger SP
  • Journal Title: Nat Commun Volume: 3 Pages: 948
  • DOI: DOI:10.1038/ncomms1948
  • Peer Reviewed
• [Journal Article] Radiotherapy promotes tumor-specific effector CD8+ T cells via dendritic cell activation (2012)
  • Author(s): Gupta A, Probst HC, Vuong V, Landshammer A, Muth S, Yagita H, Schwendener R, Pruschy M, Knuth A, van den Broek M
  • Journal Title: J Immunol Volume: 189 Pages: 558-566
  • DOI: DOI: 10.4049/jimmunol.1200563
  • Peer Reviewed
• [Journal Article] Radiotherapy increases the permissiveness of established mammary tumors to rejection by immunomodulatory antibodies (2012)
  • Author(s): Verbrugge I, Hagekyriakou J, Sharp LL, Galli M, West AC, McLaughlin NM, Duret H, Yagita H, Johnstone RW, Smyth MJ, Haynes NM
  • Journal Title: Cancer Res Volume: 72 Pages: 3163-3174
  • DOI: DOI:10.1158/0008-5472.CAN-12-0210
  • Peer Reviewed
• [Journal Article] Cancer-induced immunosuppression: IL-18-elicited immunoablative NK cells (2012)
  • Author(s): Terme M, Ullrich E, Aymeric L, Meinhardt K, Coudert J, Desbois M, Ghiringhelli F, Viaud S, Ryffel B, Yagita H, Chen L, Mecheri S, Kaplanski G, Prevost-Blondel A, Kato M, Schultze JL, Tartour E, Kroemer G, Degli-Esposti M, Chaput N, Zitvogel L
  • Journal Title: Cancer Res Volume: 72 Pages: 2757-2767
  • DOI: DOI:10.1158/0008-5472.CAN-11-3379
  • Peer Reviewed
• [Journal Article] Induction of pro-apoptotic antibodies to triple negative breast cancer by vaccination with TRAIL death receptor DR5 DNA (2012)
  • Author(s): Piechocki MP, Wu GS, Jones RF, Jacob JB, Gibson H, Ethier SP, Abrams1 J, Yagita H, Venuprasad K, Wei WZ
  • Journal Title: Int J Cancer Volume: 131 Pages: 2562-2572
  • DOI: DOI:10.1002/ijc.27534
  • Peer Reviewed
• [Journal Article] ATM-mediated DNA damage signals mediate immune escape through integrin αVβ3-dependent mechanisms (2012)
  • Author(s): Jinushi M, Chiba S, Baghdadi M, Kinoshita I, Dosaka-Akita H, Yoshiyama H, Yagita H, Uede T, Takaoka A
  • Journal Title: Cancer Res Volume: 72 Pages: 56-65
  • DOI: DOI:10.1158/0008-5472.CAN-11-2028
  • Peer Reviewed
• [Journal Article] Aging-associated B7-DC(+) B cells enhance anti-tumor immunity via Th1 and Th17 induction (2012)
  • Author(s): Tomihara K, Shin T, Hurez VJ, Yagita H, Pardoll DM, Zhang B, Curiel TJ, Shin T
  • Journal Title: Aging Cell Volume: 11 Pages: 128-138
  • DOI: DOI:10.1111/j.1474-9726.2011.00764.x
  • Peer Reviewed
• [Journal Article] Importin β1 protein-mediated nuclear localization of death receptor 5 (DR5) limits DR5/tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced cell death of human tumor cells (2011)
  • Author(s): Kojima Y, Nakayama M, Nishina T, Nakano H, Koyanagi M, Takeda K, Okumura K, Yagita H
  • Journal Title: J Biol Chem Volume: 286 Pages: 43383-43393
  • DOI: DOI:10.1074/jbc.M111.309377
  • Peer Reviewed
• [Journal Article] Tumor-associated macrophages regulate tumorigenicity and anticancer drug responses of cancer stem/initiating cells (2011)
  • Author(s): Jinushi M, Chiba S, Yoshiyama H, Masutomi K, Kinoshita I, Dosaka H, Yagita H, Takaoka A, Tahara H
  • Journal Title: Proc Natl Acad Sci USA Volume: 108 Pages: 12425-12430
  • DOI: DOI:10.1073/pnas.1106645108
  • Peer Reviewed
• [Journal Article] IL-18 induces PD-1-dependent immunosuppression in cancer (2011)
  • Author(s): Terme M, Ullrich E, Aymeric L, Meinhardt K, Desbois M, Delahaye NF, Viaud S, Ryffel B, Yagita H, Kaplanski G, Prevost-Blondel A, Kato M, Schultze JL, Tartour E, Kroemer G, Chaput N, Zitvogel L
  • Journal Title: Cancer Res Volume: 71 Pages: 5412-5422
  • DOI: DOI:10.1158/0008-5472.CAN-11-0993
  • Peer Reviewed
• [Journal Article] Development and characterization of a potent immunoconjugate targeting the Fn14 receptor on solid tumor cells (2011)
  • Author(s): Zhou H, Marks JW, Hittelman WN, Yagita H, Cheung LH, Rosenblum MG, Winkles JA
  • Journal Title: Mol Cancer Ther Volume: 10 Pages: 1276-1288
  • DOI: DOI:0.1158/1535-7163.MCT-11-0161
  • Peer Reviewed
• [Journal Article] Combination of lentivector immunization and low dose chemotherapy or PD-1/PD-L1 blocking primes self-reactive T cells and induces anti-tumor immunity (2011)
  • Author(s): Sierro SR, Donda A, Perret R, Guillaume P, Yagita H, Levy F, Romero P
  • Journal Title: Eur J Immunol Volume: 41 Pages: 2217-2228
  • DOI: DOI:10.1002/eji.201041235
  • Peer Reviewed
• [Journal Article] TLR2-dependent induction of IL-10 and Foxp3+CD25+CD4+ regulatory T cells prevents effective anti-tumor immunity induced by Pam2 lipopeptides in vivo (2011)
  • Author(s): Yamazaki S, Okada K, Maruyama A, Matsumoto M, Yagita H, Seya T
  • Journal Title: PLoS One Volume: 6(4) Pages: e18833
  • DOI: DOI:10.1371/journal.pone.0018833
  • Peer Reviewed
• [Journal Article] Anti-ErbB-2 mAb therapy requires type I and II interferons and synergizes with anti-PD-1 or anti-CD137 mAb therapy (2011)
  • Author(s): Stagg J, Loi S, Divisekera U, Ngiow SF, Duret H, Yagita H, Teng MW, Smyth MJ
  • Journal Title: Proc Natl Acad Sci USA Volume: 108 Pages: 7142-7147
  • DOI: DOI:10.1073/pnas.1016569108
  • Peer Reviewed
• [Journal Article] FOXO3 programs tumor-associated DCs to become tolerogenic in human and murine prostate cancer (2011)
  • Author(s): Watkins SK, Zhu Z, Riboldi E, Shafer-Weaver KA, Stagliano KE, Sklavos MM, Ambs S, Yagita H, Hurwitz AA
  • Journal Title: J Clin Invest Volume: 121 Pages: 1361-1372
  • DOI: DOI:10.1172/JCI44325
  • Peer Reviewed
• [Journal Article] Anti-TIM3 antibody promotes T cell IFN-γ-mediated anti-tumor immunity and suppresses established tumors (2011)
  • Author(s): Ngiow SF, von Scheidt B, Akiba H, Yagita H, Teng MW, Smyth MJ
  • Journal Title: Cancer Res Volume: 71 Pages: 3540-3551
  • DOI: DOI: 10.1158/0008-5472.CAN-11-0096
  • Peer Reviewed
• [Journal Article] Epigenetic modulation enhances the therapeutic effect of anti-IL13Ralpha2 antibody in human mesothelioma xenografts (2011)
  • Author(s): Takenouchi M, Hirai S, Sakuragi N, Yagita H, Hamada H, Kato K
  • Journal Title: Clin Cancer Res Volume: 17 Pages: 2819-2829
  • DOI: DOI:10.1158/1078-0432.CCR-10-2986
  • Peer Reviewed
• [Journal Article] Anti-tumor activities and on-target toxicities mediated by TRAIL receptor agonist following co-treatment with panobinostat (2011)
  • Author(s): Martin BP, J Frew A, Bots M, Fox S, Long F, Takeda K, Yagita H, Atadja P, Smyth MJ, Johnstone RW
  • Journal Title: Int J Cancer Volume: 128 Pages: 2735-2747
  • DOI: DOI:10.1002/ijc.25594
  • Peer Reviewed
• [Journal Article] Therapeutic potential of the TWEAK/Fn14 pathway in intractable gastrointestinal cancer (2011)
  • Author(s): Yoriki R, Akashi S, Sho M, Nomi T, Yamato I, Hotta K, Takayama T, Matsumoto S, Wakatsuki K, Migita K, Yagita H, Nakajima Y
  • Journal Title: Exp Ther Med Volume: 2 Pages: 103-108
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/22977477
  • Peer Reviewed
• [Journal Article] Blockade of programmed death-1 pathway rescues the effector function of tumor-infiltrating T cells and enhances the antitumor efficacy of lentivector immunization (2010)
  • Author(s): Zhou Q, Xiao H, Liu Y, Peng Y, Hong Y, Yagita H, Chandler P, Munn DH, Mellor A, Fu N, He Y
  • Journal Title: J Immunol Volume: 185 Pages: 5082-5092
  • DOI: DOI:10.4049/jimmunol.1001821
  • Peer Reviewed
• [Journal Article] Spatiotemporal basis of CTLA-4 costimulatory molecule-mediated negative regulation of T cell activation (2010)
  • Author(s): Yokosuka T, Kobayashi W, Takamatsu M, Sakata-Sogawa K, Zeng H, Hashimoto-Tane A, Yagita H, Tokunaga M, Saito T
  • Journal Title: Immunity Volume: 33 Pages: 326-339
  • DOI: DOI:10.1016/j.immuni.2010.09.006
  • Peer Reviewed
• [Journal Article] Control of established melanoma by CD27 stimulation is associated with enhanced effector function and persistence,and reduced PD-1 expression of tumor infiltrating CD8+ T cells (2010)
  • Author(s): Roberts DJ, Franklin NA, Kingeter LM, Yagita H, Tutt AL, Glennie MJ, Bullock TN
  • Journal Title: J Immunother Volume: 33 Pages: 769-779
  • DOI: DOI:10.1097/CJI.0b013e3181ee238f
  • Peer Reviewed
• [Journal Article] Peptide vaccine induces enhanced tumor growth associated with apoptosis induction in CD8+ T cells (2010)
  • Author(s): Muraoka D, Kato T, Wang L, Maeda Y, Noguchi T, Harada N, Takeda K, Yagita H, Guillaume P, Luescher I, Old LJ, Shiku H, Nishikawa H
  • Journal Title: J Immunol Volume: 185 Pages: 3768-3776
  • DOI: DOI:10.4049/jimmunol.0903649
  • Peer Reviewed
• [Journal Article] Darcy PK, Smyth MJ: CD11c+ dendritic cells and B cells contribute to the tumoricidal activity of anti-DR5 antibody therapy in established tumors (2010)
  • Author(s): Haynes NM, Hawkins ED, Li M, McLaughlin NM, Hammerling GJ, Schwendener R, Winoto A, Wensky A, Yagita H, Takeda K, Kershaw MH
  • Journal Title: J Immunol Volume: 185 Pages: 532-541
  • DOI: DOI:10.4049/jimmunol.0903624
  • Peer Reviewed
• [Journal Article] Combination therapy of established tumors by antibodies targeting immune activating and suppressing molecules (2010)
  • Author(s): Takeda K, Kojima Y, Uno T, Hayakawa Y, Teng MWL, Yoshizawa H, Yagita H, Geyjo F, Okumura K, Smyth MJ
  • Journal Title: J Immunol Volume: 184 Pages: 5493-5501
  • DOI: DOI:10.4049/jimmunol.0903033
  • Peer Reviewed
• [Journal Article] Notch2 signaling is required for potent antitumor immunity in vivo (2010)
  • Author(s): Sugimoto K, Maekawa Y, Kitamura A, Nishida J, Koyanagi A, Yagita H, Kojima H, Chiba S, Shimada M, Yasutomo K
  • Journal Title: J Immunol Volume: 184 Pages: 4673-4678
  • DOI: DOI:10.4049/jimmunol.0903661
  • Peer Reviewed
• [Journal Article] Optimized combination therapy using bortezomib, TRAIL and TLR agonists in established breast tumors (2010)
  • Author(s): Lee S, Yagita H, Sayers TJ, Celis E
  • Journal Title: Cancer Immunol Immunother Volume: 59 Pages: 1073-1081
  • DOI: DOI:10.1007/s00262-010-0834-0
  • Peer Reviewed
• [Journal Article] lockade of delta-like ligand 4 signaling inhibits both growth and angiogenesis of pancreatic cancer (2010)
  • Author(s): Oishi H, Sunamura M. Egawa S, Motoi F, Unno M, Furukawa T, Habib NA, Yagita H
  • Journal Title: Pancreas Volume: 39 Pages: 897-903
  • DOI: DOI:10.1097/MPA.0b013e3181ce7185
  • Peer Reviewed
• [Journal Article] Anti-tumor effects of depleting and non-depleting anti-CD27 monoclonal antibodies in immune-competent mice (2010)
  • Author(s): Sakanishi T, Yagita H
  • Journal Title: Biochem Biophys Res Commun Volume: 393 Pages: 829-835
  • DOI: DOI:10.1016/j.bbrc.2010.02.092
  • Peer Reviewed
• [Journal Article] PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors (2010)
  • Author(s): Curran MA, Montalvo W, Yagita H, Allison JP
  • Journal Title: Proc Natl Acad Sci USA Volume: 107 Pages: 4275-4280
  • DOI: DOI:10.1016/j.bbrc.2010.02.092
  • Peer Reviewed
• [Journal Article] Tumor-reactive CD4+ T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts (2010)
  • Author(s): Quezada SA, Simpson TR, Peggs KS, Merghoub T, Vider J, Fan X, Blasberg R, Yagita H, Muranski P, Antony PA, Restifo NP, Allison JP
  • Journal Title: J Exp Med Volume: 207 Pages: 637-650
  • DOI: DOI:10.1084/jem.20091918
  • Peer Reviewed
• [Journal Article] DNAM-1/CD155 interactions promote cytokine NK cell-mediated suppression of poorly immunogenic melanoma metastasis (2010)
  • Author(s): Chan CJ, Andrew DM, McLaughlin NM, Yagita H, Gilfillan S, Colonna M, Smyth MJ
  • Journal Title: J Immunol Volume: 184 Pages: 902-911
  • DOI: DOI:10.4049/jimmunol.0903225
  • Peer Reviewed