title: Betting on immunotherapy for melanoma.
abstract: 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.
authors.affiliation: Yale Cancer Center, 333 Cedar Street, FMP #126, New Haven, CT 06525, USA. Mario.sznol@yale.edu
authors.forename: Mario
authors.initials: M
authors.lastname: Sznol
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D000074324:Ipilimumab
references.citation: Immunol Rev. 2008 Apr;222:206-21
references.pmid: 18364004
references.citation: Nat Med. 2004 Sep;10(9):909-15
references.pmid: 15340416
references.citation: Nat Rev Cancer. 2007 Feb;7(2):95-106
references.pmid: 17251916
references.citation: Immunol Rev. 2008 Aug;224:166-82
references.pmid: 18759926
references.citation: Nat Rev Cancer. 2008 Apr;8(4):299-308
references.pmid: 18354418
references.citation: J Immunother. 2003 Jul-Aug;26(4):332-42
references.pmid: 12843795
references.citation: Eur J Immunol. 2009 Mar;39(3):883-93
references.pmid: 19224637
references.citation: Clin Cancer Res. 2008 Sep 1;14(17):5610-8
references.pmid: 18765555
references.citation: Cancer Immunol Immunother. 2009 May;58(5):823-30
references.pmid: 19198837
references.citation: J Immunol. 2006 May 1;176(9):5255-66
references.pmid: 16621991
references.citation: Clin Cancer Res. 2004 Mar 1;10(5):1670-7
references.pmid: 15014018
references.citation: J Clin Oncol. 2008 Nov 10;26(32):5233-9
references.pmid: 18809613
references.citation: J Exp Med. 2005 Jan 3;201(1):139-48
references.pmid: 15630141
references.citation: N Engl J Med. 2008 Jun 19;358(25):2698-703
references.pmid: 18565862
references.citation: J Clin Oncol. 1999 Jul;17(7):2105-16
references.pmid: 10561265
references.citation: Immunol Rev. 2006 Oct;213:131-45
references.pmid: 16972901
references.citation: N Engl J Med. 2004 Sep 2;351(10):998-1012
references.pmid: 15342808
references.citation: Cancer Res. 2007 Feb 15;67(4):1832-41
references.pmid: 17308126
references.citation: Nat Med. 2007 Dec;13(12):1440-9
references.pmid: 18026115
references.citation: J Exp Med. 2001 Aug 20;194(4):481-9
references.pmid: 11514604
references.citation: Cancer Immunol Immunother. 2007 Jan;56(1):101-9
references.pmid: 16485126
references.citation: Nature. 2002 Oct 17;419(6908):734-8
references.pmid: 12384702
references.citation: Clin Cancer Res. 2006 Apr 1;12(7 Pt 2):2353s-2358s
references.pmid: 16609058
references.citation: J Clin Oncol. 2008 Feb 1;26(4):527-34
references.pmid: 18235113
references.citation: Nat Rev Immunol. 2007 Jan;7(1):41-51
references.pmid: 17186030
references.citation: J Clin Immunol. 2008 Nov;28(6):647-59
references.pmid: 18792765
references.citation: Science. 2008 Oct 10;322(5899):271-5
references.pmid: 18845758
references.citation: Cell. 2008 May 30;133(5):775-87
references.pmid: 18510923
references.citation: Ann Surg Oncol. 2005 Dec;12(12):1005-16
references.pmid: 16283570
references.citation: J Exp Med. 2004 Mar 15;199(6):815-24
references.pmid: 15024047
references.citation: Nat Med. 2006 Mar;12(3):335-41
references.pmid: 16474399
references.citation: Immunity. 2008 Mar;28(3):414-24
references.pmid: 18342010
references.citation: Nat Med. 1999 Jun;5(6):677-85
references.pmid: 10371507
references.citation: J Clin Oncol. 2007 Mar 1;25(7):876-83
references.pmid: 17327609
references.citation: Blood. 2008 Mar 15;111(6):3116-25
references.pmid: 18202224
references.citation: Blood. 2008 Jul 15;112(2):362-73
references.pmid: 18354038
references.citation: J Natl Cancer Inst. 1994 Aug 3;86(15):1159-66
references.pmid: 8028037
references.citation: Nat Med. 2008 Jan;14(1):28-36
references.pmid: 18157142
references.citation: Oncologist. 2008;13 Suppl 4:10-5
references.pmid: 19001146
references.citation: Nat Med. 2002 Aug;8(8):793-800
references.pmid: 12091876
references.citation: Science. 2006 Oct 6;314(5796):126-9
references.pmid: 16946036
references.citation: Immunol Rev. 2002 Oct;188:43-50
references.pmid: 12445280
references.citation: Immunity. 2008 Sep 19;29(3):319-24
references.pmid: 18799140
references.citation: Adv Immunol. 2006;90:51-81
references.pmid: 16730261
references.citation: Immunol Rev. 2008 Apr;222:162-79
references.pmid: 18364001
references.citation: Eur J Immunol. 2007 Jun;37(6):1678-90
references.pmid: 17492620
references.citation: Eur J Immunol. 1995 Nov;25(11):3053-9
references.pmid: 7489743
references.citation: Clin Cancer Res. 2007 Nov 15;13(22 Pt 1):6681-8
references.pmid: 17982122