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Blood, Vol. 95 No. 5 (March 1), 2000:
pp. 1781-1787
Vaccination of patients with chronic myelogenous leukemia with
bcr-abl oncogene breakpoint fusion peptides generates specific immune
responses
J. Pinilla-Ibarz,
K. Cathcart,
T. Korontsvit,
S. Soignet,
M. Bocchia,
J. Caggiano,
L. Lai,
J. Jimenez,
J. Kolitz, and
D. A. Scheinberg
From the Department of Medicine, Memorial Sloan Kettering Cancer
Center, New York, and Northshore University Hospital, Manhasset, NY.
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.
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