Expression of her-2/neu on acute lymphoblastic leukemias: implications for the development of immunotherapeutic approaches.
Her-2/neu is a tumor-associated antigen that is expressed on several adenocarcinomas and correlates with poor prognosis. In a previous study (H. J. Bühring et al., Blood, 86: 1916-1923, 1995), it has been demonstrated that Her-2/neu expression can be detected on blast cells from patients with hematological malignancies including acute lymphoblastic leukemia (ALL). Here, we show that Her-2/neu-specific CTLs induced in vitro using peptide-pulsed dendritic cells efficiently lyse primary ALL blasts constitutively expressing both Her-2/neu and human leukocyte antigen A2 in an antigen-specific and MHC-restricted manner. Furthermore, we analyzed the feasibility of this approach in an autologous setting and induced Her-2/neu-specific CTLs using dendritic cells generated from peripheral blood mononuclear cells from an ALL patient that were pulsed with peptides or transfected with in vitro-transcribed Her-2/neu mRNA. Our data demonstrate that Her-2/neu could be used as a potential target for the application of Her-2/neu-directed treatment strategies in ALL including vaccination approaches.
Müller
Martin R
MR
Department of Hematology, Oncology, and Immunology, University of Tübingen, D-72076 Tübingen, Germany.
Grünebach
Frank
F
Kayser
Katrin
K
Vogel
Wichard
W
Nencioni
Alessio
A
Brugger
Wolfram
W
Kanz
Lothar
L
Brossart
Peter
P
D018952:Antigens, CD34 / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000378:metabolism; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000378:metabolism; D018274:Electroporation; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000096:biosynthesis; D006412:Hematopoietic Stem Cells; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection
D018952:Antigens, CD34; D019496:Cancer Vaccines; D015789:HLA-A2 Antigen; D007371:Interferon-gamma; D010455:Peptides; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases