Vaccination with synthetic analog peptides derived from WT1 oncoprotein induces T-cell responses in patients with complete remission from acute myeloid leukemia.
A pilot study was undertaken to assess the safety, activity, and immunogenicity of a polyvalent Wilms tumor gene 1 (WT1) peptide vaccine in patients with acute myeloid leukemia in complete remission but with molecular evidence of WT1 transcript. Patients received 6 vaccinations with 4 WT1 peptides (200 microg each) plus immune adjuvants over 12 weeks. Immune responses were evaluated by delayed-type hypersensitivity, CD4+ T-cell proliferation, CD3+ T-cell interferon-gamma release, and WT1 peptide tetramer staining. Of the 9 evaluable patients, 7 completed 6 vaccinations and WT1-specific T-cell responses were noted in 7 of 8 patients. Three patients who were HLA-A0201-positive showed significant increase in interferon-gamma-secreting cells and frequency of WT1 tetramer-positive CD8+ T cells. Three patients developed a delayed hypersensitivity reaction after vaccination. Definite related toxicities were minimal. With a mean follow-up of 30 plus or minus 8 months after diagnosis, median disease-free survival has not been reached. These preliminary data suggest that this polyvalent WT1 peptide vaccine can be administered safely to patients with a resulting immune response. Further studies are needed to establish the role of vaccination as viable postremission therapy for acute myeloid leukemia.
Maslak
Peter G
PG
Leukemia Service, Department of Medicine, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. maslakp@mskcc.org
Dao
Tao
T
Krug
Lee M
LM
Chanel
Suzanne
S
Korontsvit
Tatyana
T
Zakhaleva
Victoria
V
Zhang
Ronghua
R
Wolchok
Jedd D
JD
Yuan
Jianda
J
Pinilla-Ibarz
Javier
J
Berman
Ellin
E
Weiss
Mark
M
Jurcic
Joseph
J
Frattini
Mark G
MG
Scheinberg
David A
DA
D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D003602:Cytotoxicity, Immunologic; D018572:Disease-Free Survival; D005260:Female; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D015789:HLA-A2 Antigen; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015513:Oncogene Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D010865:Pilot Projects; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014611:Vaccination / Q000379:methods*; D022223:Vaccines, Subunit / Q000235:genetics / Q000276:immunology; D025721:WT1 Proteins / Q000276:immunology / Q000627:therapeutic use*; D055815:Young Adult
D019496:Cancer Vaccines; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D015513:Oncogene Proteins; D022223:Vaccines, Subunit; D025721:WT1 Proteins; D007371:Interferon-gamma
Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13885-90
15365188
Blood. 2009 Jun 25;113(26):6541-8
19389880
Blood. 2006 May 1;107(9):3481-5
16455952
Leukemia. 2005 Aug;19(8):1318-23
15920488
J Exp Med. 1998 Dec 21;188(12):2357-68
9858522
Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4547-55
17671141
Blood. 2007 Sep 15;110(6):1924-32
17505014
Blood. 2004 Feb 1;103(3):1037-42
14504104
Leukemia. 2008 Aug;22(8):1613-6
18256684
J Clin Oncol. 2008 Nov 20;26(33):5429-35
18591546
Leukemia. 2003 Dec;17(12):2318-57
14562125
Blood. 2000 Mar 1;95(5):1781-7
10688838
Leuk Res. 2006 Oct;30(10):1293-8
16533527
Cancer Immunol Immunother. 2005 Aug;54(8):721-8
16010587
Leukemia. 2007 May;21(5):868-76
17361230
Jpn J Clin Oncol. 2006 Apr;36(4):231-6
16611662
J Natl Compr Canc Netw. 2008 Nov;6(10):995-1002
19176197
Blood. 2002 Sep 15;100(6):2132-7
12200377
Blood. 2003 Oct 15;102(8):2892-900
12829610
Clin Cancer Res. 2005 Dec 15;11(24 Pt 1):8799-807
16361568
Cancer Immunol Immunother. 2006 Jul;55(7):850-60
16220325
Clin Cancer Res. 2006 Jan 1;12(1):34-42
16397021
Int J Cancer. 1998 Dec 9;78(6):740-9
9833768
J Clin Oncol. 2008 Oct 1;26(28):4595-602
18559874
J Immunol. 2000 Dec 1;165(11):6047-55
11086036
Blood. 2005 Aug 15;106(4):1415-8
15845894
Haematologica. 2005 Oct;90(10):1324-32
16219568
Blood. 2008 Jan 1;111(1):236-42
17875804