Individualized vaccination of AML patients in remission is associated with induction of antileukemia immunity and prolonged remissions

PMID: 27928025
Journal: Science translational medicine (volume: 8, issue: 368, Sci Transl Med 2016 12;8(368):368ra171)
Published: 2016-12-07

Authors:
Rosenblatt J, Stone RM, Uhl L, Neuberg D, Joyce R, Levine JD, Arnason J, McMasters M, Luptakova K, Jain S, Zwicker JI, Hamdan A, Boussiotis V, Steensma DP, DeAngelo DJ, Galinsky I, Dutt PS, Logan E, Bryant MP, Stroopinsky D, Werner L, Palmer K, Coll M, Washington A, Cole L, Kufe D, Avigan D

ABSTRACT

We developed a personalized cancer vaccine in which patient-derived acute myeloid leukemia (AML) cells are fused with autologous dendritic cells, generating a hybridoma that potently stimulates broad antitumor responses. We report results obtained from the first 17 AML patients, who achieved remission after chemotherapy and were then serially vaccinated to target minimal residual disease and prevent relapse. Vaccination was well tolerated and induced inflammatory responses at the site of administration, characterized by the dense infiltration of T cells. Vaccination was also associated with a marked rise in circulating T cells recognizing whole AML cells and leukemia-specific antigens that persisted for more than 6 months. Twelve of 17 vaccinated patients (71%; 90% confidence interval, 52 to 89%) remain alive without recurrence at a median follow-up of 57 months. The results demonstrate that personalized vaccination of AML patients in remission induces the expansion of leukemia-specific T cells and may be protective against disease relapse.