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

Kyriaki Dunussi-Joannopoulos, Howard J. Weinstein, Peter W. Nickerson, Terry B. Strom, Steven J. Burakoff, James M. Croop, Robert J. Arceci

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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.

Original languageEnglish (US)
Pages (from-to)2938-2946
Number of pages9
JournalBlood
Volume87
Issue number7
DOIs
StatePublished - Apr 1 1996

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Dunussi-Joannopoulos, K., Weinstein, H. J., Nickerson, P. W., Strom, T. B., Burakoff, S. J., Croop, J. M., & Arceci, R. J. (1996). Irradiated B7-1 transduced primary acute myelogenous leukemia (AML) cells can be used as therapeutic vaccines in murine AML. Blood, 87(7), 2938-2946. https://doi.org/10.1182/blood.v87.7.2938.bloodjournal8772938