Betting on immunotherapy for melanoma.
Immunotherapy is an effective treatment option for a small percentage of patients with advanced melanoma or at high risk for recurrence after resection of the primary tumor. However, a long period of unsuccessful immune modulation trials involving new cytokines, antibodies, cancer vaccines, adoptive immunotherapy, and combinations generated doubts that benefit could be extended to a larger group of patients. Renewed optimism for the therapeutic potential of immune therapy is currently driven by key advances in tumor immunobiology, including the potential to manipulate and disrupt immune activation checkpoints and tumor defense mechanisms; newer approaches to antigen presentation for immune activation; refinements to procedures for antigen-specific T-cell expansions in vitro and preparative regimens to support their expansion and activity in vivo; gene transfer to alter lymphocyte specificity and function; and the potential for discovery of improved predictive biomarkers to select patients for individual treatments. Proof of concept is provided by durable remissions observed in patients with advanced melanoma enrolled in clinical trials of anti-CTLA-4 and in new studies of adoptively transferred tumor antigen-specific lymphocytes combined with lymphocyte ablation conditioning regimens. Many agents now being developed are predicted to produce broader, more potent, and more effective antitumor immune responses.
Sznol
Mario
M
Yale Cancer Center, 333 Cedar Street, FMP #126, New Haven, CT 06525, USA. Mario.sznol@yale.edu
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD / Q000276:immunology; D060908:CTLA-4 Antigen; D006801:Humans; D007167:Immunotherapy / Q000379:methods* / Q000639:trends; D000074324:Ipilimumab; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D000074324:Ipilimumab
Immunol Rev. 2008 Apr;222:206-21
18364004
Nat Med. 2004 Sep;10(9):909-15
15340416
Nat Rev Cancer. 2007 Feb;7(2):95-106
17251916
Immunol Rev. 2008 Aug;224:166-82
18759926
Nat Rev Cancer. 2008 Apr;8(4):299-308
18354418
J Immunother. 2003 Jul-Aug;26(4):332-42
12843795
Eur J Immunol. 2009 Mar;39(3):883-93
19224637
Clin Cancer Res. 2008 Sep 1;14(17):5610-8
18765555
Cancer Immunol Immunother. 2009 May;58(5):823-30
19198837
J Immunol. 2006 May 1;176(9):5255-66
16621991
Clin Cancer Res. 2004 Mar 1;10(5):1670-7
15014018
J Clin Oncol. 2008 Nov 10;26(32):5233-9
18809613
J Exp Med. 2005 Jan 3;201(1):139-48
15630141
N Engl J Med. 2008 Jun 19;358(25):2698-703
18565862
J Clin Oncol. 1999 Jul;17(7):2105-16
10561265
Immunol Rev. 2006 Oct;213:131-45
16972901
N Engl J Med. 2004 Sep 2;351(10):998-1012
15342808
Cancer Res. 2007 Feb 15;67(4):1832-41
17308126
Nat Med. 2007 Dec;13(12):1440-9
18026115
J Exp Med. 2001 Aug 20;194(4):481-9
11514604
Cancer Immunol Immunother. 2007 Jan;56(1):101-9
16485126
Nature. 2002 Oct 17;419(6908):734-8
12384702
Clin Cancer Res. 2006 Apr 1;12(7 Pt 2):2353s-2358s
16609058
J Clin Oncol. 2008 Feb 1;26(4):527-34
18235113
Nat Rev Immunol. 2007 Jan;7(1):41-51
17186030
J Clin Immunol. 2008 Nov;28(6):647-59
18792765
Science. 2008 Oct 10;322(5899):271-5
18845758
Cell. 2008 May 30;133(5):775-87
18510923
Ann Surg Oncol. 2005 Dec;12(12):1005-16
16283570
J Exp Med. 2004 Mar 15;199(6):815-24
15024047
Nat Med. 2006 Mar;12(3):335-41
16474399
Immunity. 2008 Mar;28(3):414-24
18342010
Nat Med. 1999 Jun;5(6):677-85
10371507
J Clin Oncol. 2007 Mar 1;25(7):876-83
17327609
Blood. 2008 Mar 15;111(6):3116-25
18202224
Blood. 2008 Jul 15;112(2):362-73
18354038
J Natl Cancer Inst. 1994 Aug 3;86(15):1159-66
8028037
Nat Med. 2008 Jan;14(1):28-36
18157142
Oncologist. 2008;13 Suppl 4:10-5
19001146
Nat Med. 2002 Aug;8(8):793-800
12091876
Science. 2006 Oct 6;314(5796):126-9
16946036
Immunol Rev. 2002 Oct;188:43-50
12445280
Immunity. 2008 Sep 19;29(3):319-24
18799140
Adv Immunol. 2006;90:51-81
16730261
Immunol Rev. 2008 Apr;222:162-79
18364001
Eur J Immunol. 2007 Jun;37(6):1678-90
17492620
Eur J Immunol. 1995 Nov;25(11):3053-9
7489743
Clin Cancer Res. 2007 Nov 15;13(22 Pt 1):6681-8
17982122