Irradiated B7-1 transduced primary acute myelogenous leukemia (AML) cells can be used as therapeutic vaccines in murine AML

Abstract

Recent studies have shown that tumor cells genetically modified by transduction of B7–1, a natural ligand for the T-cell costimulatory molecules CD28 and CTLA-4, are rejected in syngeneic hosts. In these reports, transformed cell lines and drug-selected cells have been used for vaccinations. To determine the effectiveness of B7–1-transduced primary acute myelogenous leukemia (AML) cells on the induction of antitumor immunity, we have studied a murine AML model in which primary AML cells were retrovirally transduced with the murine B7–1 cDNA. A defective retroviral producer clone expressing B7–1 and secreting a high titer of virus was used for infection of AML cells. Unselected transduced AML cells, expressing a high level of B7–1, were used for in vivo vaccinations. Our results show that one intravenous (IV) injection of irradiated B7–1-positive (B7–1+) AML cells can provide long-lasting (5 to 6 months) systemic immunity against subsequent challenge with wild-type AML cells. Furthermore, one exposure to irradiated B7–1+ AML cells results in rejection of leukemia by leukemic mice when the vaccination occurs in the early stages of the disease. The antileukemia immunity is CD8+ T-cell-dependent and B7/CD28-mediated, since in vivo treatment of mice with anti-CD8 monoclonal antibody or CTLA-4 Ig leads to abrogation of the specific antileukemia immune response. These results emphasize that B7–1 vaccines may have therapeutic usefulness for patients with AML.