Abstract
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.
Original language | English (US) |
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Pages (from-to) | 1645-1654 |
Number of pages | 10 |
Journal | Leukemia |
Volume | 16 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2002 |
Externally published | Yes |
Keywords
- AML
- CD80
- GM-CSF
- Gene therapy
- Immunotherapy
- Lentivirus
ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research