• AML is an immunogenic malignancy known to be susceptible to lysis by leukemia antigen-specific CD8+ CTLs as well as NK cells (Schurch et al., 2013). The so-called graft-versus-leukemia effect associated with allogeneic hematopoietic stem cell transplantation (HSCT) elegantly illustrates the therapeutic role of the immune system in AML (Schurch et al., 2013). AML is therefore believed to be particularly amenable to immunotherapeutic approaches (Anguille et al., 2012c; Martner et al., 2013; Schurch et al., 2013). |
• Conventional chemotherapy followed by allogeneic HSCT is associated with significant toxicity and is therefore not feasible for older patients with AML, who represent the majority of AML patients (Anguille et al., 2012c). Their favorable toxicity profile makes immunotherapy approaches, such as DC-based immunotherapy, worthy of investigation to fill this treatment void (Anguille et al., 2011a). |
• DC therapy has already shown to be potentially useful in AML, especially when applied in a minimal residual disease (MRD) setting (i.e., a situation in which a small amount of tumor cells persists after therapy and that is responsible for tumor recurrence) (Van Tendeloo et al., 2010; Anguille et al., 2012c). This corroborates the notion that immunotherapy is most optimally applied as an adjunct therapy at early stages of cancer when only few immunosuppressive tumor cells are present (Gulley et al., 2011; Anguille et al., 2014). |
• Standard response evaluation criteria used in solid malignancies (e.g., RECIST) do not appear to capture the true clinical benefit of immunotherapy approaches (Schlom, 2012; Anguille et al., 2014). In AML, numerous surrogate end points for evaluation of treatment efficacy (e.g., molecular MRD markers) have been developed and validated for use in clinical trials, facilitating translational research (Cilloni et al., 2009; Hourigan and Karp, 2013). |