Immune Monitoring Of Vaccine Quality And Persistence Of Specific T Cell Responses In Five Aml Patients Receiving Extended Dendritic Cell Vaccination Under Compassionate Use

High rates of early disease relapse are observed in patients with acute myeloid leukemia (AML). Due to poor health status, many patients cannot tolerate intensive chemotherapy and/or stem cell transplantation, resulting in a high unmet medical need for new therapy options. Clinical benefit of SCT is associated with immune responses that can control residual leukemia. To replace SCT in non-eligible patients, we designed an autologous dendritic cell (DC) vaccine approach that is given 4 times weekly at the beginning (immunization phase) followed by booster vaccines at week six and then monthly, with the intention to induce immune responses that delay or prevent relapse. The DCs secrete bioactive IL-12, but not IL-10, allowing activation of innate and adaptive responses. T cell responses are directed to two target antigens expressed in AML: Wilm's tumor-1 (WT-1) and preferentially expressed in melanoma (PRAME). Prior to initiation of a Phase I/II study implementing this vaccine approach (EudraCT No.: 2014-003520-44; clinicaltrials.gov No.: NCT02405338), five patients were treated under compassionate use (CU) using DC vaccines prepared according to an approved GMP manufacturing protocol.