title: WT1 vaccination in AML and MDS: A pilot trial with synthetic analog peptides.
abstract: Peptide vaccines are capable of eliciting immune responses targeting tumor-associated antigens such as the Wilms' Tumor 1 (WT1) antigen, often overexpressed in myeloid malignancies. Here, we assessed the safety, tolerability, and immunogenicity of a polyvalent WT1 peptide vaccine. Individuals with WT1-positive acute myeloid leukemia (AML) in first (CR1) or second (CR2) remission or with higher-risk myelodysplastic syndrome (MDS) following at least 1 prior line of therapy were vaccinated with a mixture of peptides derived from the WT1 protein, with sargramostim injections before vaccination to amplify immunogenicity. Six vaccinations were delivered biweekly, continuing then monthly until patients received 12 vaccinations or showed disease relapse or progression. Therapeutic efficacy was evaluated by progression-free and overall survival. Immune responses were evaluated by delayed-type hypersensitivity testing and T-cell IFNγ ELISPOT at specified intervals. In 16 patients who received at least one vaccination, 10 completed the planned course of six vaccinations and six continued for up to six additional monthly vaccinations. Vaccinations were well tolerated, with no patients discontinuing due to toxicity. One of two patients with high-risk MDS experienced a prolonged decrease in transfusion dependence. Two of 14 AML patients demonstrated relapse-free survival >1 year. Both patients were in CR2 at time of vaccination, with duration of their remission exceeding duration of their first remission, suggesting a potential benefit. Our WT1 vaccine was well-tolerated. The clinical benefit that we observed in several patients suggests engagement of a protective immune response, indicating a need for further trials.
authors: Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Jason
authors: J
authors: Brayer
authors: Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.|Department of Oncologic Sciences, University of South Florida, Tampa, Florida.
authors: Jeffrey E
authors: JE
authors: Lancet
authors: Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: John
authors: J
authors: Powers
authors: Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.|Department of Oncologic Sciences, University of South Florida, Tampa, Florida.
authors: Alan
authors: A
authors: List
authors: Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.|Department of Oncologic Sciences, University of South Florida, Tampa, Florida.
authors: Lodovico
authors: L
authors: Balducci
authors: Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.|Department of Oncologic Sciences, University of South Florida, Tampa, Florida.
authors: Rami
authors: R
authors: Komrokji
authors: Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.|Department of Oncologic Sciences, University of South Florida, Tampa, Florida.|Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Javier
authors: J
authors: Pinilla-Ibarz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000627:therapeutic use*; D005260:Female; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000175:diagnosis / Q000276:immunology / Q000473:pathology; D007117:Immunization, Secondary; D007155:Immunologic Factors / Q000008:administration & dosage; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D010455:Peptides / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000276:immunology; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000008:administration & dosage; D012074:Remission Induction; D016019:Survival Analysis; D014611:Vaccination; D022223:Vaccines, Subunit; D025721:WT1 Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D007155:Immunologic Factors; D010455:Peptides; D011994:Recombinant Proteins; D022223:Vaccines, Subunit; D025721:WT1 Proteins; C583751:WT1 protein, human; C081222:sargramostim; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor