Source:http://linkedlifedata.com/resource/pubmed/id/10688838
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2000-3-29
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| pubmed:abstractText |
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 microg, 150 microg, 500 microg, or 1500 microg total peptide mixed with 100 microg QS-21 as an immunological adjuvant. Delayed-type hypersensitivity (DTH), humoral responses, and unprimed ex vivo autologous proliferation ((3)H-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. (Blood. 2000;95:1781-1787)
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Mar
|
| pubmed:issn |
0006-4971
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
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| pubmed:volume |
95
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1781-7
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| pubmed:dateRevised |
2007-11-15
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| pubmed:meshHeading |
pubmed-meshheading:10688838-Adjuvants, Immunologic,
pubmed-meshheading:10688838-Adult,
pubmed-meshheading:10688838-Aged,
pubmed-meshheading:10688838-Amino Acid Sequence,
pubmed-meshheading:10688838-Cancer Vaccines,
pubmed-meshheading:10688838-Clonal Anergy,
pubmed-meshheading:10688838-Dose-Response Relationship, Immunologic,
pubmed-meshheading:10688838-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:10688838-Female,
pubmed-meshheading:10688838-Fusion Proteins, bcr-abl,
pubmed-meshheading:10688838-Humans,
pubmed-meshheading:10688838-Hypersensitivity, Delayed,
pubmed-meshheading:10688838-Immunization, Passive,
pubmed-meshheading:10688838-Leukemia, Myelogenous, Chronic, BCR-ABL Positive,
pubmed-meshheading:10688838-Male,
pubmed-meshheading:10688838-Middle Aged,
pubmed-meshheading:10688838-Molecular Sequence Data,
pubmed-meshheading:10688838-Peptide Fragments,
pubmed-meshheading:10688838-Safety,
pubmed-meshheading:10688838-Sequence Alignment,
pubmed-meshheading:10688838-T-Lymphocytes, Cytotoxic,
pubmed-meshheading:10688838-Treatment Outcome,
pubmed-meshheading:10688838-Vaccination
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| pubmed:year |
2000
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| pubmed:articleTitle |
Vaccination of patients with chronic myelogenous leukemia with bcr-abl oncogene breakpoint fusion peptides generates specific immune responses.
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| pubmed:affiliation |
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
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| pubmed:publicationType |
Journal Article,
Clinical Trial,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|