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

• Published in: Blood Vol. 95; no. 5; pp. 1781 - 1787
• Main Authors: Pinilla-Ibarz, J., Cathcart, K., Korontsvit, T., Soignet, S., Bocchia, M., Caggiano, J., Lai, L., Jimenez, J., Kolitz, J., Scheinberg, D.A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2000
• Subjects: Adjuvants, Immunologic; Adult; Aged; Amino Acid Sequence; Cancer Vaccines - administration & dosage; Cancer Vaccines - adverse effects; Cancer Vaccines - immunology; Clonal Anergy; Dose-Response Relationship, Immunologic; Enzyme-Linked Immunosorbent Assay; Female; Fusion Proteins, bcr-abl - administration & dosage; Fusion Proteins, bcr-abl - immunology; Humans; Hypersensitivity, Delayed - immunology; Immunization, Passive - adverse effects; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - immunology; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - therapy; Male; Middle Aged; Molecular Sequence Data; Peptide Fragments - administration & dosage; Peptide Fragments - immunology; Safety; Sequence Alignment; T-Lymphocytes, Cytotoxic - immunology; Treatment Outcome; Vaccination
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V95.5.1781.005k46_1781_1787

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.