Vaccination of patients with chronic myelogenous leukemia with bcr-abl oncogene breakpoint fusion peptides generates specific immune responses Journal Article

Authors: Pinilla-Ibarz, J.; Cathcart, K.; Korontsvit, T.; Soignet, S.; Bocchia, M.; Caggiano, J ; Lai, L.; Jimenez, J.; Kolitz, J.; Scheinberg, D. A.
Article Title: Vaccination of patients with chronic myelogenous leukemia with bcr-abl oncogene breakpoint fusion peptides generates specific immune responses
Abstract: Chronic myelogenous leukemia (CML) presents a unique opportunity to develop therapeutic strategies using vaccination against a truly tumor- specific antigen that is also the oncogenic protein required for neoplasia. CML is characterized by the t(9;22) that results in the bcr-abl fusion oncogene and in the expression of a chimeric protein product p210. Previously we have shown that peptides derived from amino acid sequences crossing the b3a2 fusion breakpoint in p210 elicit class I restricted cytotoxic T lymphocytes and class II responses, respectively, in vitro. Such sequences may thus comprise absolutely tumor-specific antigens in a peptide-based vaccine. We evaluated the safety and immunogenicity of a multidose, bcr-abl breakpoint peptide vaccine in 12 adults with chronic-phase CML. Cohorts of 3 patients each received either 50 μg, 150 μg, 500 μg, or 1500 μg total peptide mixed with 100 μg QS-21 as an immunological adjuvant. Delayed-type hypersensitivity (DTH), humoral responses, and unprimed ex vivo autologous proliferation (3H-thymidine incorporation) and cytotoxicity (chromium-51 release) responses were measured. All 68 vaccinations were well tolerated without significant adverse effects. In 3 of the 6 patients treated at the 2 highest dose levels of vaccine, peptide-specific, T-cell proliferative responses (n = 3) and/or DTH responses (n = 2) were generated that lasted up to 5 months after vaccination. Cytotoxic T lymphocytes have not been identified. In conclusion, a tumor-specific, bcr-abl derived peptide vaccine can be safely administered to patients with chronic-phase CML and can elicit a bcr-abl peptide-specific immune response despite the presence of active disease in these patients and approximately 1012 leukemia cells. (C) 2000 by The American Society of Hematology.
Keywords: adult; clinical article; treatment outcome; aged; middle aged; hydroxyurea; clinical trial; alpha interferon; lymphocyte proliferation; gene expression; cytotoxicity; chronic myeloid leukemia; tumor antigen; enzyme linked immunosorbent assay; oncogene; immune response; amino acid sequence; molecular sequence data; hybrid protein; cancer vaccine; cancer vaccines; sequence alignment; peptide fragments; vaccination; t-lymphocytes, cytotoxic; immunological adjuvant; safety; enzyme-linked immunosorbent assay; adjuvants, immunologic; fusion proteins, bcr-abl; qs 21; delayed hypersensitivity; synthetic peptide; hypersensitivity, delayed; chronic leukemia; immunization, passive; leukemia, myeloid, philadelphia-positive; clonal anergy; dose-response relationship, immunologic; humans; human; male; female; priority journal; article
Journal Title: Blood
Volume: 95
Issue: 5
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2000-03-01
Start Page: 1781
End Page: 1787
Language: English
PUBMED: 10688838
PROVIDER: scopus
Notes: Export Date: 18 November 2015 -- Source: Scopus