DC-Based Vaccines Show in-Vitro Activity against Chronic Myeloid Leukemia Cells

Abstract

Chronic Myeloid leukemia is a common myeloproliferative disease. Despite recent advances in targeted therapy, only 7–12% of patients achieve molecular remission. Leukemic cells arrange multiple mechanisms to avoid recognition by the immune system. Dendritic cells (DC) are professional antigen presenting cells of the immune system playing a crucial role in the induction of anti-tumor responses. The use of DC is an attractive immunotherapeutic strategy against cancers, especially in minimal residual disease state. In this study, DC vaccine against chronic myeloid leukemia was generated and evaluated in-vitro. Monocytes were isolated and enriched from peripheral blood. These monocytes were subsequently cultured in RPMI medium supplemented with GM-CSF and IL-4 to induce them to become DC. These DC were then co-cultured with tumor lysates obtained from CML cell line in culture medium supplemented with GM-CSF, IL-4 and TNF alpha to become DC-based CML vaccine. The generated DC-based CML vaccines retained their DC morphology, showed strong expression of CD 86 and HLA-DR, and were negative for CD14. Mixed lymphocyte reaction indicated that the generated DC-based CML vaccines were capable of inducing proliferative responses to allogeneic lymphocytes. DC-based CML vaccines were shown to stimulate T cells to express DC-ligands, ie CD28 and CD154, as well as HLA-DR, CD71 and CD 25. In addition, the stimulated T cells were cytotoxic to CML cells used to prepare tumor lysates.