Transduction of acute myeloid leukemia cells with third generation self-inactivating lentiviral vectors expressing CD80 and GM-CSF: effects on proliferation, differentiation, and stimulation of allogeneic and autologous anti-leukemia immune responses

Leukemia. 2002 Sep;16(9):1645-54. doi: 10.1038/sj.leu.2402582.


Acute myeloid leukemia (AML) patients treated with available therapies achieve remission in approximately 60% of cases, but the long-term event-free survival is less than 30%. Use of immunotherapy during remission is a potential approach to increase survival. We propose to develop cell vaccines by genetic modification of AML cells with CD80, an essential T cell costimulator that is lacking in the majority of AML cases, and GM-CSF, to induce proliferation and activation of professional antigen-presenting cells. Here, we evaluated third generation self inactivating (SIN) lentiviral vectors, which have the potential advantage of improved safety. CD80 and GM-CSF expression by these vectors was higher than that reported with second generation vectors (Stripecke et al, Blood 2000; 96: 1317-1326). In some cases, endogenous GM-CSF expression by transduced AML cells induced phenotypic changes consistent with the maturation of leukemia blasts into antigen-presenting cells. Further, in all cases studied, GM-CSF expression was associated with higher proliferation and cell viability. Allogeneic and autologous mixed lymphocyte reactions performed with transduced irradiated AML cells expressing CD80 and/or GM-CSF demonstrated that expression of either transgene enhanced T cell activation. These pre-clinical data demonstrate the potential feasibility of third generation SIN vectors for use in AML immunotherapy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Adult
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • B7-1 Antigen / genetics*
  • B7-1 Antigen / metabolism
  • Cell Differentiation
  • Cell Division
  • Cytotoxicity, Immunologic / genetics
  • Flow Cytometry
  • Genetic Therapy*
  • Genetic Vectors
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics*
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Lentivirus / genetics*
  • Leukemia, Myeloid / genetics*
  • Leukemia, Myeloid / immunology*
  • Leukemia, Myeloid / pathology
  • Lymphocyte Activation
  • Lymphocyte Culture Test, Mixed
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Transduction, Genetic
  • Tumor Cells, Cultured


  • Antigens, CD
  • B7-1 Antigen
  • Granulocyte-Macrophage Colony-Stimulating Factor