Identification of HLA-A*0201-presented T cell epitopes derived from the oncofetal antigen-immature laminin receptor protein in patients with hematological malignancies.
The oncofetal Ag immature laminin receptor (OFA-iLR) is a potential target molecule for immunotherapeutic studies in several tumor entities, including hematological malignancies. In the present study, we characterize two HLA-A*0201-presented epitopes eliciting strong OFA-iLR peptide-specific human cytotoxic T cell (CTLs) responses in vitro. Both allogeneic HLA-A*0201-matched and autologous CTLs recognized and killed endogenously OFA-iLR-expressing tumor cell lines and primary malignant cells from patients with hemopoietic malignancies in an MHC-restricted fashion but spared nonmalignant hemopoietic cells. Spontaneous OFA-iLR peptide-specific T cell reactivity was detectable in a significant proportion of leukemia patients. Interestingly, in patients with chronic lymphocytic leukemia and multiple myeloma but not in those with acute myeloid leukemia, significant frequencies of OFA peptide-specific CTLs could be detected in an early stage of disease but disappeared in patients with progressive disease. The identification of OFA-iLR-derived peptide epitopes provides a basis for tumor immunological studies and therapeutic vaccination strategies in patients with OFA-iLR-expressing malignancies.
Siegel
Sandra
S
General Hospital St. Georg, Department of Hematology, Hamburg, Germany.
Wagner
Andreas
A
Friedrichs
Birte
B
Wendeler
Anneke
A
Wendel
Lena
L
Kabelitz
Dieter
D
Steinmann
Jörg
J
Barsoum
Adel
A
Coggin
Joseph
J
Rohrer
James
J
Dreger
Peter
P
Schmitz
Norbert
N
Zeis
Matthias
M
D000328:Adult; D000368:Aged; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology / Q000378:metabolism*; D015789:HLA-A2 Antigen; D006801:Humans; D020014:K562 Cells; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D017474:Receptors, Laminin / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012269:Ribosomal Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014162:Transfection
D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; C510624:RPSA protein, human; D017474:Receptors, Laminin; D012269:Ribosomal Proteins; C509834:immature laminin receptor protein, mouse; C031192:oncofetal antigens