Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-4-14
pubmed:abstractText
The receptor for hyaluronic acid-mediated motility (RHAMM) is a tumor-associated antigen in chronic lymphocytic leukemia (CLL). CD8(+) T cells primed with the RHAMM-derived epitope R3, which is restricted by human leukocyte antigen (HLA)-A2, effectively lyse RHAMM(+) CLL cells. Therefore, we initiated a phase I clinical trial of R3 peptide vaccination. Six HLA-A2(+) CLL patients were vaccinated four times at biweekly intervals with the R3 peptide (ILSLELMKL; 300 microg per dose) emulsified in incomplete Freund's adjuvant; granulocyte-macrophage colony stimulating factor (100 microg per dose) was administered concomitantly. Detailed immunological analyses were conducted throughout the course of peptide vaccination. No severe adverse events greater than CTC I degrees skin toxicity were observed. Four patients exhibited reduced white blood cell counts during vaccination. In five of six patients, R3-specific CD8(+) T cells were detected with the corresponding peptide/HLA-A2 tetrameric complex; these populations were verified functionally in four of five patients using enzyme-linked immunosorbent spot (ELISpot) assays. In patients with clinical responses, we found increased frequencies of R3-specific CD8(+) T cells that expressed high levels of CD107a and produced both interferon-gamma and granzyme B in response to antigen challenge. Interestingly, vaccination was also associated with the induction of regulatory T cells in four patients. Thus peptide vaccination in six CLL patients was safe and could elicit to some extent specific CD8(+) T-cell responses against the tumor antigen RHAMM.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1476-5551
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
798-805
pubmed:meshHeading
pubmed-meshheading:20220777-Adult, pubmed-meshheading:20220777-Aged, pubmed-meshheading:20220777-Antigens, CD44, pubmed-meshheading:20220777-CD8-Positive T-Lymphocytes, pubmed-meshheading:20220777-Cancer Vaccines, pubmed-meshheading:20220777-Cell Proliferation, pubmed-meshheading:20220777-Epitopes, T-Lymphocyte, pubmed-meshheading:20220777-Extracellular Matrix Proteins, pubmed-meshheading:20220777-Feasibility Studies, pubmed-meshheading:20220777-Female, pubmed-meshheading:20220777-Flow Cytometry, pubmed-meshheading:20220777-HLA-A2 Antigen, pubmed-meshheading:20220777-Humans, pubmed-meshheading:20220777-Immunotherapy, pubmed-meshheading:20220777-Interferon-gamma, pubmed-meshheading:20220777-Leukemia, Lymphocytic, Chronic, B-Cell, pubmed-meshheading:20220777-Lymphocyte Count, pubmed-meshheading:20220777-Male, pubmed-meshheading:20220777-Middle Aged, pubmed-meshheading:20220777-Peptide Fragments, pubmed-meshheading:20220777-T-Lymphocytes, Cytotoxic, pubmed-meshheading:20220777-T-Lymphocytes, Regulatory, pubmed-meshheading:20220777-Vaccination
pubmed:year
2010
pubmed:articleTitle
Peptide vaccination elicits leukemia-associated antigen-specific cytotoxic CD8+ T-cell responses in patients with chronic lymphocytic leukemia.
pubmed:affiliation
Clinical Immunology Department, Medical University of Lublin, Lublin, Poland. giannop@tlen.pl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Clinical Trial, Phase I