Immune responses and long‐term disease recurrence status after telomerase‐based dendritic cell immunotherapy in patients with acute myeloid leukemia. Issue 16 (14th April 2017)

• Record Type: Journal Article
• Authors: Khoury, Hanna J.; Collins, Robert H.; Blum, William; Stiff, Patrick S.; Elias, Laurence; Lebkowski, Jane S.; Reddy, Anita; Nishimoto, Kevin P.; Sen, Debasish; Wirth, Edward D.; Case, Casey C.; DiPersio, John F.
• Is Part Of: Cancer. Volume 123:Issue 16(2017)
• Page Start: 3061
• Page End: 3072
• Publication Date: 2017-04-14
• Subjects: acute myeloid leukemia (AML) -- dendritic cells -- human telomerase reverse transcriptase (hTERT) -- immunotherapy -- recurrence‐free survival -- T cells -- telomerase; Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.30696
• Languages: English
• ISSNs: 0008-543X

Abstract

Abstract : BACKGROUND: Telomerase activity in leukemic blasts frequently is increased among patients with high‐risk acute myeloid leukemia (AML). In the current study, the authors evaluated the feasibility, safety, immunogenicity, and therapeutic potential of human telomerase reverse transcriptase (hTERT)‐expressing autologous dendritic cells (hTERT‐DCs) in adult patients with AML. METHODS: hTERT‐DCs were produced from patient‐specific leukapheresis, electroporated with an mRNA‐encoding hTERT and a lysosomal‐targeting sequence, and cryopreserved. A total of 22 patients with a median age of 58 years (range, 30‐75 years) with intermediate‐risk or high‐risk AML in first or second complete remission (CR) were enrolled. hTERT‐DCs were generated for 24 patients (73%). A median of 17 intradermal vaccinations (range, 6‐32 intradermal vaccinations) containing 1×10 7 cells were administered as 6 weekly injections followed by 6 biweekly injections. A total of 21 patients (16 in first CR, 3 in second CR, and 2 with early disease recurrence) received hTERT‐DCs. RESULTS: hTERT‐DCs were well tolerated with no severe toxicities reported, with the exception of 1 patient who developed idiopathic thrombocytopenic purpura. Of the 19 patients receiving hTERT‐DCs in CR, 11 patients (58%) developed hTERT‐specific T‐cell responses that primarily were targeted toward hTERT peptides with predicted low human leukocyte antigen (HLA)‐binding affinities. With a median follow‐up of 52 months, 58% of patients in CR (11 of 19 patients) were free of disease recurrence at the time of their last follow‐up visit; 57% of the patients who were aged ≥60 years (4 of 7 patients) also were found to be free of disease recurrence at a median follow‐up of 54 months. CONCLUSIONS: The generation of hTERT‐DCs is feasible and vaccination with hTERT‐DCs appears to be safe and may be associated with favorable recurrence‐free survival. Cancer 2017;123:3061–72. © 2017 American Cancer Society . Abstract : The administration of telomerase‐pulsed dendritic cells leads to antitelomerase T‐cell responses in patients with intermediate‐risk and high‐risk acute myeloid leukemia. Approximately 58% of patients with acute myeloid leukemia were found to remain free of disease recurrence with a median follow‐up of 52 months, thereby suggesting possible favorable recurrence‐free survival.