Expression of costimulatory molecules in human leukemias.
In order to determine the indication of B7 (B7-1 and B7-2) molecules-mediated immuno-gene therapy for human leukemias, we investigated 94 human leukemic samples for the expression of MHC molecules required for tumor antigen-specific signals and of B7-1, B7-2, and ICAM-1 molecules required for non-specific costimulatory signals. All samples were strongly positive for MHC class I and 84% for class II antigen. B7-1, B7-2 and ICAM-1 were expressed in 5%, 22% and 16% of the total cases, respectively. Especially in 54 AML samples, B7-1 was only expressed in one case, while B7-2 was detected in as many as 15 cases (28%). We have also examined 13 human myelo/monocytic cell lines for the expression of class II and costimulatory molecules and found that significant expression of costimulatory molecules was induced in human leukemic cells by some suitable drugs, among which interferon-gamma (IFN-gamma) was the most potent inducer. Our results indicate that when the B7-mediated immuno-gene therapy was applied to human leukemias, especially to AML, B7-1 was rather preferable to B7-2 in that the latter was more widely expressed on human leukemic cells. Furthermore, since gene-transfer systems occasionally accompany serious problems, it should be taken into account that costimulatory molecules on human myelo/monocytic leukemic cells could be induced ex vivo without the introduction of exogenous genes.
Hirano
N
N
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Takahashi
T
T
Takahashi
T
T
Ohtake
S
S
Hirashima
K
K
Emi
N
N
Saito
K
K
Hirano
M
M
Shinohara
K
K
Takeuchi
M
M
Taketazu
F
F
Tsunoda
S
S
Ogura
M
M
Omine
M
M
Saito
T
T
Yazaki
Y
Y
Ueda
R
R
Hirai
H
H
D015703:Antigens, CD / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D005260:Female; D005434:Flow Cytometry; D015316:Genetic Therapy; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D007938:Leukemia / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D007951:Leukemia, Myeloid / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000276:immunology
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma