title: A clinical and immunologic phase 2 trial of Wilms tumor gene product 1 (WT1) peptide vaccination in patients with AML and MDS.
abstract: This study investigated the immunogenicity of Wilms tumor gene product 1 (WT1)-peptide vaccination in WT1-expressing acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients without curative treatment option. Vaccination consisted of granulocyte-macrophage colony-stimulating factor subcutaneously days 1 to 4, and WT1.126-134 peptide and 1 mg keyhole limpet hemocyanin on day 3. The initial 9 patients received 4 vaccinations biweekly, then monthly, and the subsequent 10 patients received continual biweekly vaccination. Seventeen AML patients and 2 refractory anemia with excess blasts patients received a median of 11 vaccinations. Treatment was well tolerated. Objective responses in AML patients were 10 stable diseases (SDs) including 4 SDs with more than 50% blast reduction and 2 with hematologic improvement. An additional 4 patients had clinical benefit after initial progression, including 1 complete remission and 3 SDs. WT1 mRNA levels decreased at least 3-fold from baseline in 35% of patients. In 8 of 18 patients, WT1-tetramer(+) T cells increased in blood and in 8 of 17 patients in bone marrow, with a median frequency in bone marrow of 0.18% at baseline and 0.41% in week 18. This WT1 vaccination study provides immunologic, molecular, and preliminary evidence of potential clinical efficacy in AML patients, warranting further investigations.
authors.affiliation: Department of Hematology and Oncology, Charité Campus Benjamin Franklin, Hindenburgdamm 30, Berlin, Germany. ulrich.keilholz@charite.de
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keilholz
authors.forename: Anne
authors.initials: A
authors.lastname: Letsch
authors.forename: Antonia
authors.initials: A
authors.lastname: Busse
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Asemissen
authors.forename: Sandra
authors.initials: S
authors.lastname: Bauer
authors.forename: Igor Wolfgang
authors.initials: IW
authors.lastname: Blau
authors.forename: Wolf-Karsten
authors.initials: WK
authors.lastname: Hofmann
authors.forename: Lutz
authors.initials: L
authors.lastname: Uharek
authors.forename: Eckhard
authors.initials: E
authors.lastname: Thiel
authors.forename: Carmen
authors.initials: C
authors.lastname: Scheibenbogen
mesh_terms: D000208:Acute Disease; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000368:Aged; D000369:Aged, 80 and over; D000754:Anemia, Refractory, with Excess of Blasts / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D004890:Erythema / Q000209:etiology; D005260:Female; D016162:Genes, Wilms Tumor; D006801:Humans; D007115:Immunization Schedule; D016233:Immunotherapy, Active / Q000009:adverse effects; D007271:Injections, Intradermal; D007279:Injections, Subcutaneous; D007951:Leukemia, Myeloid / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D016879:Salvage Therapy; D037182:T-Cell Antigen Receptor Specificity; D025721:WT1 Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C543100:WT1 (126-134), human; D025721:WT1 Proteins