EXPRESSION OF COSTIMULATORY MOLECULES IN HUMAN LEUKEMIAS

In order to determine the indication of B7 (B7-1 and B7-2) molecules-m ediated immune-gene therapy for human leukemias, we investigated 94 hu man 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 str ongly 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, res pectively. Especially in 54 AML samples, B7-1 was only expressed in on e 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 o f class II and costimulatory molecules and found that significant expr ession of costimulatory molecules was induced in human leukemic cells by some suitable drugs, among which interferon-gamma (IFN-gamma) was t he most potent inducer. Our results indicate that when the B7-mediated immune-gene therapy was applied to human leukemias, especially to AML , B7-1 was rather preferable to B7-2 in that the latter was more widel y expressed on human leukemic cells. Furthermore, since gene-transfer systems occasionally accompany serious problems, it should be taken in to account that costimulatory molecules on human myelo/monocytic leuke mic cells could be induced ex vivo without the introduction of exogeno us genes.