Immunotherapy for myeloid leukemias: current status and future directions

Abstract

Myeloid leukemias, although a heterogeneous group of hematopoietic stem cell neoplasms, are arguably among the most suited for active specific immunotherapy. Nevertheless, clinical development of myeloid leukemia vaccine lagged behind similar approaches in other solid and hematological malignancies. The recent identification of apparently specific leukemia antigens and advances in understanding the fundamentals of tumor immunology have helped initiate a number of early phase clinical studies evaluating the safety and clinical efficacy of this approach. Here we review the recently identified and characterized putative leukemia antigens, the main vaccination strategies employed by most investigators and the results of clinical studies of immunotherapy of myeloid leukemias. Although these studies are early and often difficult to interpret, they offer evidence that effective immunity to leukemia could be induced following vaccination, and that clinical benefit can sometimes be observed, thus setting the stage for future development of this strategy and in the combinatorial approaches to treatment of myeloid leukemias that incorporate immunotherapy.

Figure 1

Cross-presentation of tumor-associated antigen by patient-derived antigen presenting dendritic cells. (a) Autologous or allogeneic tumor cells are transfected with the gene for granulocyte-macrophage colony-stimulating factor (GM-CSF); (b) irradiated GM-CSF producing cells are injected into patients; (c) local production of GM-CSF helps to induce the recruitment and maturation of dendritic cells; (d) dendritic cells process and cross-present shed antigen from tumor cells to antigen-specific T cells; (e) primed T cells proliferate and migrate to sites of tumor.