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Irradiated B7-1 transduced primary acute myelogenous leukemia (AML) cells
can be used as therapeutic vaccines in murine AML
K Dunussi-Joannopoulos, HJ Weinstein, PW Nickerson, TB Strom, SJ Burakoff, JM Croop and RJ Arceci
Dana-Farber Cancer Institute, Department of Pediatrics, Boston, MA 02115
USA.
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.
Volume 87,
Issue 7,
pp. 2938-2946,
04/01/1996
Copyright © 1996 by The American Society of Hematology
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