PMID- 20220777
OWN - NLM
STAT- MEDLINE
DCOM- 20100520
LR  - 20220129
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Linking)
VI  - 24
IP  - 4
DP  - 2010 Apr
TI  - Peptide vaccination elicits leukemia-associated antigen-specific cytotoxic CD8+ 
      T-cell responses in patients with chronic lymphocytic leukemia.
PG  - 798-805
LID - 10.1038/leu.2010.29 [doi]
AB  - 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.
FAU - Giannopoulos, K
AU  - Giannopoulos K
AD  - Clinical Immunology Department, Medical University of Lublin, Lublin, Poland. 
      giannop@tlen.pl
FAU - Dmoszynska, A
AU  - Dmoszynska A
FAU - Kowal, M
AU  - Kowal M
FAU - Rolinski, J
AU  - Rolinski J
FAU - Gostick, E
AU  - Gostick E
FAU - Price, D A
AU  - Price DA
FAU - Greiner, J
AU  - Greiner J
FAU - Rojewski, M
AU  - Rojewski M
FAU - Stilgenbauer, S
AU  - Stilgenbauer S
FAU - Dohner, H
AU  - Dohner H
FAU - Schmitt, M
AU  - Schmitt M
LA  - eng
GR  - G0501963/MRC_/Medical Research Council/United Kingdom
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100311
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Cancer Vaccines)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Hyaluronan Receptors)
RN  - 0 (Peptide Fragments)
RN  - 0 (hyaluronan-mediated motility receptor)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adult
MH  - Aged
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cancer Vaccines/immunology/*therapeutic use
MH  - Cell Proliferation
MH  - Epitopes, T-Lymphocyte
MH  - Extracellular Matrix Proteins/*immunology
MH  - Feasibility Studies
MH  - Female
MH  - Flow Cytometry
MH  - HLA-A2 Antigen/immunology/metabolism
MH  - Humans
MH  - Hyaluronan Receptors/*immunology
MH  - Immunotherapy
MH  - Interferon-gamma/metabolism
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*immunology/therapy
MH  - Lymphocyte Count
MH  - Male
MH  - Middle Aged
MH  - Peptide Fragments/immunology/*therapeutic use
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - T-Lymphocytes, Regulatory/immunology
MH  - Vaccination
EDAT- 2010/03/12 06:00
MHDA- 2010/05/21 06:00
CRDT- 2010/03/12 06:00
PHST- 2010/03/12 06:00 [entrez]
PHST- 2010/03/12 06:00 [pubmed]
PHST- 2010/05/21 06:00 [medline]
AID - leu201029 [pii]
AID - 10.1038/leu.2010.29 [doi]
PST - ppublish
SO  - Leukemia. 2010 Apr;24(4):798-805. doi: 10.1038/leu.2010.29. Epub 2010 Mar 11.