Enhancement of lytic activity of leukemic cells by CD8+ cytotoxic T lymphocytes generated against a WT1 peptide analogue.
The Wilms tumor antigen 1 (WT1) antigen is over-expressed in human leukemias, making it an attractive target for immunotherapy. Most WT1-specific Cytotoxic T Lymphocytes (CTLs) described so far displayed low avidity, limiting its function. To improve the immunogenicity of CTL epitopes, we replaced the first-amino-acid of two known immunogenic WT1-peptides (126 and 187) with a tyrosine. This modification enhances 126Y analogue-binding ability, triggers significant number of IFN-gamma-producing T cells (P = 0.0003), induces CTL that cross-react with the wild-type peptide, exerts a significant lytic activity against peptide-loaded-targets (P = 0.0006) and HLA-A0201-matched-leukemic cells (P = 0.0014). These data support peptide modification as a feasible approach for the development of a leukemia-vaccine.
Al Qudaihi
Ghofran
G
Tumor Immunology Section, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
Lehe
Cynthia
C
Negash
Muna
M
Al-Alwan
Monther
M
Ghebeh
Hazem
H
Mohamed
Said Yousuf
SY
Saleh
Abu-Jafar Mohammed
AJ
Al-Humaidan
Hind
H
Tbakhi
Abdelghani
A
Dickinson
Anne
A
Aljurf
Mahmoud
M
Dermime
Said
S
D040761:Biomimetic Materials / Q000378:metabolism*; D045744:Cell Line, Tumor; D000939:Epitopes / Q000276:immunology; D015234:HLA-A Antigens / Q000276:immunology / Q000378:metabolism; D015789:HLA-A2 Antigen; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007938:Leukemia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology*; D025721:WT1 Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D000939:Epitopes; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D025721:WT1 Proteins; D007371:Interferon-gamma