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
[1]   T-cell regulation by CD28 and CTLA-4 [J].
Alegre, ML ;
Frauwirth, KA ;
Thompson, CB .
NATURE REVIEWS IMMUNOLOGY, 2001, 1 (03) :220-228
[2]   ANALYSIS OF SURVIVAL BY TUMOR RESPONSE [J].
ANDERSON, JR ;
CAIN, KC ;
GELBER, RD .
JOURNAL OF CLINICAL ONCOLOGY, 1983, 1 (11) :710-719
[3]  
[Anonymous], J CLIN ONCOLOGY
[4]  
[Anonymous], J CLIN ONCOLOGY S18
[5]   Phase I Study of Ipilimumab, an Anti-CTLA-4 Monoclonal Antibody, in Patients with Relapsed and Refractory B-Cell Non-Hodgkin Lymphoma [J].
Ansell, Stephen M. ;
Hurvitz, Sara A. ;
Koenig, Patricia A. ;
LaPlant, Betsy R. ;
Kabat, Brian F. ;
Fernando, Donna ;
Habermann, Thomas M. ;
Inwards, David J. ;
Verma, Meena ;
Yamada, Reiko ;
Erlichman, Charles ;
Lowy, Israel ;
Timmerman, John M. .
CLINICAL CANCER RESEARCH, 2009, 15 (20) :6446-6453
[6]   High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: Analysis of 270 patients treated between 1985 and 1993 [J].
Atkins, MB ;
Lotze, MT ;
Dutcher, JP ;
Fisher, RI ;
Weiss, G ;
Margolin, K ;
Abrams, J ;
Sznol, M ;
Parkinson, D ;
Hawkins, M ;
Paradise, C ;
Kunkel, L ;
Rosenberg, SA .
JOURNAL OF CLINICAL ONCOLOGY, 1999, 17 (07) :2105-2116
[7]  
Atkins MB, 2000, CANCER J SCI AM, V6, pS11
[8]   Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4 [J].
Attia, P ;
Phan, GQ ;
Maker, AV ;
Robinson, MR ;
Quezado, MM ;
Yang, JC ;
Sherry, RM ;
Topalian, SL ;
Kammula, US ;
Royal, RE ;
Restifo, NP ;
Haworth, LR ;
Levy, C ;
Mavroukakis, SA ;
Nichol, G ;
Yellin, MJ ;
Rosenberg, SA .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (25) :6043-6053
[9]   CLINICAL USE OF BIOLOGIC RESPONSE MODIFIERS IN CANCER-TREATMENT - AN OVERVIEW .2. COLONY-STIMULATING FACTORS AND INTERLEUKIN-2 [J].
BALMER, CM .
DICP-THE ANNALS OF PHARMACOTHERAPY, 1991, 25 (05) :490-498
[10]  
BARTH A, 1995, J AM COLL SURGEONS, V181, pA193