Generation of functional dendritic cells (DC) in adult acute lymphoblastic leukemia: rationale for a DC-based vaccination program for patients in complete hematological remission

Abstract

The capacity to generate effective dendritic cells (DC) from adult acute lymphoblastic leukemia (ALL) patients in complete remission (CR) and off-therapy was investigated. Monocyte-derived DC cultured in the presence of granulocyte-macrophage colony-stimulating factor, interleukin (IL)-4 and tumor necrosis factor (TNF)-α expressed maturation markers, produced IL-12 and loaded apoptotic bodies to a similar extent to normal DC. Patients' circulating T and NK lymphocytes were normally represented and, after stimulation, were capable of producing TNF-α and interferon-γ to a similar extent to control lymphocytes. DC loaded with leukemia-derived apoptotic bodies increased their ability to stimulate both allogeneic and autologous lymphocytes, and to generate specific anti-leukemic CD3 + cells. These findings offer a rationale for the design of DC-based vaccine programs for adult ALL patients in CR with the aim of controlling/eradicating the disease.

Keywords:

• Acute lymphoblastic leukemia
• dendritic cells
• immunotherapy
• anti-leukemic specific lymphocytes
• immunomodulant cytokines
• loading of apoptotic bodies