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

被引:190
作者
Pinilla-Ibarz, J
Cathcart, K
Korontsvit, T
Soignet, S
Bocchia, M
Caggiano, J
Lai, L
Jimenez, J
Kolitz, J
Scheinberg, DA
机构
[1] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA
[2] Northshore Univ Hosp, Manhasset, NY USA
关键词
D O I
10.1182/blood.V95.5.1781.005k46_1781_1787
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 mu g, 150 mu g, 500 mu g, or 1500 mu g total peptide mixed with 100 mu g QS-21 as an immunological adjuvant, Delayed-type hypersensitivity (DTH), humoral responses, and unprimed ex vivo autologous proliferation (H-3-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 10(12) leukemia cells. (C) 2000 by The American Society of Hematology.
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页码:1781 / 1787
页数:7
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