Current Experience With CTLA4-blocking Monoclonal Antibodies for the Treatment of Solid Tumors

被引:29
作者
Agarwala, Sanjiv S. [1 ]
Ribas, Antoni [2 ]
机构
[1] St Lukes Canc Ctr, Dept Hematol & Oncol, Bethlehem, PA 18015 USA
[2] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Med, Div Hematol Oncol, Los Angeles, CA 90024 USA
关键词
oncology; anti-CTLA4; mAb; ipilimumab; tremelimumab; immunotherapy; LYMPHOCYTE-ASSOCIATED ANTIGEN-4; REGULATORY T-CELLS; PHASE-I TRIAL; CTLA-4; BLOCKADE; METASTATIC MELANOMA; TREMELIMUMAB CP-675,206; COMBINATION IMMUNOTHERAPY; PROSTATE-CANCER; INDOLEAMINE 2,3-DIOXYGENASE; TRYPTOPHAN CATABOLISM;
D O I
10.1097/CJI.0b013e3181dcd260
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Monoclonal antibodies (mAbs) specific for cytotoxic T lymphocyte-associated antigen 4 (CTLA4) are a novel form of immunotherapy for treatment of patients with advanced cancers. These anti-CTLA4 mAbs prevent normal downregulation of the immune system, thus prolonging and enhancing T-cell activation and potentially promoting an antitumor immune response. Clinical studies in patients with advanced cancers have indicated that CTLA4 blockade with mAbs is associated with antitumor activity in a small percentage of patients and has a manageable toxicity profile. The key limitations for broader applicability of this mode of therapy are better definition of the mechanism that leads to tumor rejection and the validation of favorable observations in single-arm studies into prospectively randomized clinical trials.
引用
收藏
页码:557 / 569
页数:13
相关论文
共 127 条
[91]  
ODAY SJ, 2008, J CLIN ONCOL S, V26, pS488
[92]   Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma [J].
Phan, GQ ;
Yang, JC ;
Sherry, RM ;
Hwu, P ;
Topalian, SL ;
Schwartzentruber, DJ ;
Restifo, NP ;
Haworth, LR ;
Seipp, CA ;
Freezer, LJ ;
Morton, KE ;
Mavroukakis, SA ;
Duray, PH ;
Steinberg, SM ;
Allison, JP ;
Davis, TA ;
Rosenberg, SA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (14) :8372-8377
[93]   Limited tumor infiltration by activated T effector cells restricts the therapeutic activity of regulatory T cell depletion against established melanoma [J].
Quezada, Sergio A. ;
Peggs, Karl S. ;
Simpson, Tyler R. ;
Shen, Yuelei ;
Littman, Dan R. ;
Allison, James P. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2008, 205 (09) :2125-2138
[94]  
RALPH C, 2008, AM ASS CANC RES AACR
[95]   Biologic and immunomodulatory events after CTLA-4 blockade with ticilimumab in patients with advanced malignant melanoma [J].
Reuben, JM ;
Lee, BN ;
Li, CP ;
Gomez-Navarro, J ;
Bozon, VA ;
Parker, CA ;
Hernandez, IM ;
Gutierrez, C ;
Lopez-Berestein, G ;
Camacho, LH .
CANCER, 2006, 106 (11) :2437-2444
[96]   Role of dendritic cell phenotype, determinant spreading, and negative costimulatory blockade in dendritic cell-based melanoma immunotherapy [J].
Ribas, A ;
Glaspy, JA ;
Lee, YH ;
Dissette, VB ;
Seja, E ;
Vu, HT ;
Tchekmedyian, NS ;
Oseguera, D ;
Comin-Anduix, B ;
Wargo, JA ;
Amarnani, SN ;
McBride, WH ;
Economou, JS ;
Butterfield, LH .
JOURNAL OF IMMUNOTHERAPY, 2004, 27 (05) :354-367
[97]   Antitumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206 [J].
Ribas, A ;
Camacho, LH ;
Lopez-Berestein, G ;
Pavlov, D ;
Bulanhagui, CA ;
Millham, R ;
Comin-Anduix, B ;
Reuben, JM ;
Seja, E ;
Parker, CA ;
Sharma, A ;
Glaspy, JA ;
Gomez-Navarro, J .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (35) :8968-8977
[98]  
RIBAS A, 2008, AM ASS CANC RES AACR
[99]  
Ribas A, 2008, J CLIN ONCOL S, V26, p485s
[100]   Tremelimumab (CP-675,206), a cytotoxic T lymphocyte-associated antigen 4 blocking monoclonal antibody in clinical development for patients with cancer [J].
Ribas, Antoni ;
Hanson, Douglas C. ;
Noe, Dennis A. ;
Millham, Robert ;
Guyot, Deborah J. ;
Bernstein, Steven H. ;
Canniff, Paul C. ;
Sharma, Amarnath ;
Gomez-Navarro, Jesus .
ONCOLOGIST, 2007, 12 (07) :873-883