Allogeneic cellular immunotherapy for chronic B-cell leukemia

Hoogendoorn, M.

Allogeneic stem cell transplantation (SCT) following reduced-intensity conditioning (RIC) as treatment modality has curative potential in patients suffering from chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL), illustrating susceptibility of these leukemic cells for the graft-versus-leukemia (GvL) effect. However, effectiveness of this therapy is limited due to low immunogenicity of leukemic cells and the lack of specificity resulting in concurrent development of graft-versus-host-disease. Both CLL and MCL cells lack expression of costimulatory molecules necessary for an efficient immune response and thus may escape from T-cell mediated reactivity. To improve the specificity of the immune response, primary CLL or MCL cells were successfully modified into antigen-presenting cells (APC) by CD40 stimulation in the presence of cytokines. In contrast to primary malignant cells as stimulator cells, these malignant APC were capable of inducing the generation of CLL- or MCL...Show moreAllogeneic stem cell transplantation (SCT) following reduced-intensity conditioning (RIC) as treatment modality has curative potential in patients suffering from chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL), illustrating susceptibility of these leukemic cells for the graft-versus-leukemia (GvL) effect. However, effectiveness of this therapy is limited due to low immunogenicity of leukemic cells and the lack of specificity resulting in concurrent development of graft-versus-host-disease. Both CLL and MCL cells lack expression of costimulatory molecules necessary for an efficient immune response and thus may escape from T-cell mediated reactivity. To improve the specificity of the immune response, primary CLL or MCL cells were successfully modified into antigen-presenting cells (APC) by CD40 stimulation in the presence of cytokines. In contrast to primary malignant cells as stimulator cells, these malignant APC were capable of inducing the generation of CLL- or MCL-reactive cytotoxic T cell (CTL) clones from HLA-identical donors. These CTL clones effectively recognized and killed the primary leukemia and other patient-derived targets but not donor-derived targets indicating that these clones were minor histocompatibility antigen-specific. These results allow the development of new cellular immunotherapeutic interventions to further exploit the GvL effect following allogeneic SCT.Show less

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Allogeneic cellular immunotherapy for chronic B-cell leukemia