General AML

Can Personalized Vaccines induce Prolonged Remission against AML?

Dendritic cell (DC)-based immunotherapy is a favourable strategy for the elimination of minimal residual disease in patients with Acute Myeloid Leukemia (AML). The basis of this therapy is to employ the patients’ own immune cells to target and destroy the leukemic cells whilst minimising toxic side effects. It is thought that the vaccine induces the expansion of leukemia-specific T- cells which could potentially be protective against AML disease relapse.

Rosenblatt J and colleagues developed acancer vaccine in which patient-derived AML cells were fused with autologous DCs.  The safety and efficacy of this DC cancer vaccine in preventing relapse were evaluated in 17 AML patients whom had achieved remission after chemotherapy. This study was published on December 7th 2016 in Science Translational Medicine.

Despite the small sample size, there were some promising results observed. The authors reported that 12/ 17 (71%) vaccinated patients were still alive without any relapse at a median follow-up of 57 months. In addition, the vaccine was well tolerated.

Moreover, the results of this study have provided further evidence for the development of personalized anti-cancer therapy. David Avigan, M.D, one of the investigators from the Cancer Vaccine Program at the Beth Israel Deaconess Medical Center in Boston, made the following statement about the findings of the study “We're using the whole tumor cell, and that allows us to stimulate a response that's broad, that's against multiple targets, and that's against targets that are unique to that individual patient".

 

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.

References
  1. Rosenblatt J. et al. Individualized vaccination of AML patients in remission is associated with induction of antileukemia immunity and prolonged remissions. Sci Transl Med. 2016 Dec 7; 8(368): 368ra171.