Engagement of the ICOS pathway markedly enhances efficacy of CTLA-4 blockade in cancer immunotherapy

被引：245

作者：

Fan, Xiaozhou ^{[1
]}

Quezada, Sergio A. ^{[3
]}

Sepulveda, Manuel A. ^{[5
,6
]}

Sharma, Padmanee ^{[1
,2
,4
]}

Allison, James P. ^{[1
,4
,5
,6
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA

[3] UCL, Dept Res Haematol, Canc Immunol Unit, Inst Canc, London WC1E 6DD, England

[4] Mem Sloan Kettering Canc Ctr, Ludwig Ctr Canc Immunotherapy, New York, NY 10065 USA

[5] Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, New York, NY 10065 USA

[6] Mem Sloan Kettering Canc Ctr, Immunol Program, New York, NY 10065 USA

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2014年 / 211卷 / 04期

基金：

美国国家卫生研究院;

关键词：

REGULATORY T-CELLS; COMBINATION IMMUNOTHERAPY; IPILIMUMAB; EFFECTOR; EXPANSION; RESPONSES; THERAPY; TUMORS;

D O I：

10.1084/jem.20130590

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Cytotoxic T lymphocyte antigen-4 (CTLA-4) blockade with a monoclonal antibody yields durable responses in a subset of cancer patients and has been approved by the FDA as a standard therapy for late-stage melanoma. We recently identified inducible co-stimulator (ICOS) as a crucial player in the antitumor effects of CTLA-4 blockade. We now show that concomitant CTLA-4 blockade and ICOS engagement by tumor cell vaccines engineered to express ICOS ligand enhanced antitumor immune responses in both quantity and quality and significantly improved rejection of established melanoma and prostate cancer in mice. This study provides strong support for the development of combinatorial therapies incorporating anti-CTLA-4 and ICOS engagement.

引用

页码：715 / 725

页数：11

共 27 条

[1]

Potent activity of soluble B7RP-1-FC in therapy of murine tumors in syngeneic hosts [J].

Ara, G ;

Baher, A ;

Storm, N ;

Horan, T ;

Baikalov, C ;

Brisan, E ;

Camacho, R ;

Moore, A ;

Goldman, H ;

Kohno, T ;

Cattley, RC ;

Van, G ;

Gaida, K ;

Zhang, M ;

Whoriskey, JS ;

Fong, D ;

Yoshinaga, SK .

INTERNATIONAL JOURNAL OF CANCER, 2003, 103 (04) :501-507

[2]

Preoperative CTLA-4 Blockade: Tolerability and Immune Monitoring in the Setting of a Presurgical Clinical Trial [J].

Carthon, Bradley C. ;

Wolchok, Jedd D. ;

Yuan, Jianda ;

Kamat, Ashish ;

Tang, Derek S. Ng ;

Sun, Jingjing ;

Ku, Geoffrey ;

Troncoso, Patricia ;

Logothetis, Christopher J. ;

Allison, James P. ;

Sharma, Padmanee .

CLINICAL CANCER RESEARCH, 2010, 16 (10) :2861-2871

[3]

Tumor Vaccines Expressing Flt3 Ligand Synergize with CTLA-4 Blockade to Reject Preimplanted Tumors [J].

Curran, Michael A. ;

Allison, James P. .

CANCER RESEARCH, 2009, 69 (19) :7747-7755

[4]

Foster BA, 1997, CANCER RES, V57, P3325

[5]

The ICOS/ICOSL Pathway Is Required for Optimal Antitumor Responses Mediated by Anti-CTLA-4 Therapy [J].

Fu, Tihui ;

He, Qiuming ;

Sharma, Padmanee .

CANCER RESEARCH, 2011, 71 (16) :5445-5454

[6]

CD28-MEDIATED SIGNALING CO-STIMULATES MURINE T-CELLS AND PREVENTS INDUCTION OF ANERGY IN T-CELL CLONES [J].

HARDING, FA ;

MCARTHUR, JG ;

GROSS, JA ;

RAULET, DH ;

ALLISON, JP .

NATURE, 1992, 356 (6370) :607-609

[7]

Improved Survival with Ipilimumab in Patients with Metastatic Melanoma [J].

Hodi, F. Stephen ;

O'Day, Steven J. ;

McDermott, David F. ;

Weber, Robert W. ;

Sosman, Jeffrey A. ;

Haanen, John B. ;

Gonzalez, Rene ;

Robert, Caroline ;

Schadendorf, Dirk ;

Hassel, Jessica C. ;

Akerley, Wallace ;

van den Eertwegh, Alfons J. M. ;

Lutzky, Jose ;

Lorigan, Paul ;

Vaubel, Julia M. ;

Linette, Gerald P. ;

Hogg, David ;

Ottensmeier, Christian H. ;

Lebbe, Celeste ;

Peschel, Christian ;

Quirt, Ian ;

Clark, Joseph I. ;

Wolchok, Jedd D. ;

Weber, Jeffrey S. ;

Tian, Jason ;

Yellin, Michael J. ;

Nichol, Geoffrey M. ;

Hoos, Axel ;

Urba, Walter J. .

NEW ENGLAND JOURNAL OF MEDICINE, 2010, 363 (08) :711-723

[8]

ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28 [J].

Hutloff, A ;

Dittrich, AM ;

Beier, KC ;

Eljaschewitsch, B ;

Kraft, R ;

Anagnostopoulos, I ;

Kroczek, RA .

NATURE, 1999, 397 (6716) :263-266

[9]

CD28 AND CTLA-4 HAVE OPPOSING EFFECTS ON THE RESPONSE OF T-CELLS TO STIMULATION [J].

KRUMMEL, MF ;

ALLISON, JP .

JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 182 (02) :459-465

[10]

Enhancement of antitumor immunity by CTLA-4 blockade [J].

Leach, DR ;

Krummel, MF ;

Allison, JP .

SCIENCE, 1996, 271 (5256) :1734-1736

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