The role of peptide and DNA vaccines in myeloid leukemia immunotherapy

While chemotherapy and targeted therapy are successful at inducing myeloid leukemia remission, the disease remains largely incurable. We have come to realize that immunotherapy may result in a cure for the disease [1-5]. The goal of immunotherapy in myeloid leukemia is to boost the patient immune system or confer immunity with T cells, dendritic cells (DC), NK cells or monoclonal antibodies.Myeloid leukemia vaccines are most likely beneficial for eradicating minimal residual disease after chemotherapy or targeted therapy [6] although the suppressed immune status of patients who receive these treatments may influence their vaccine response. However, targeted immunotherapy using leukemia vaccines has been heavily investigated because these vaccines elicit specific immune responses against leukemia cells while sparing normal tissue. Optimal immunotherapy target antigens are leukemia-specific antigens that are exclusively expressed by leukemia cells, are absent in normal tissues, and can elicit potent immune responses; however, with the exception of the BCR-ABL and PML-RARα fusion proteins, such leukemia-specific antigens are rare in other myeloid leukemias. Leukemia-associated antigens (LAAs), such as Wilms’ tumor 1 (WT1) antigen, proteinase-3 peptide, preferentially expressed antigen of melanoma (PRAME), and receptor for hyaluronic acid-mediated motility (RHAMM), are preferentially expressed by leukemia cells but are also expressed by normal tissues, albeit to a lesser degree [7].Peptide vaccines have been developed against tumor-specific and leukemia-associated self-antigens. Numerous clinical trials involving peptide vaccines have been performed with limited success [8-11]. It has become clear that exogenous peptides alone fail to activate effective CD8+ T cell levels, and if induced, they tend to be transient in patients with a weakened or tolerized immune system. Therefore, DNA vaccines present an attractive, alternative strategy for peptide vaccination [12-15].DN