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Cancer. 2017 Aug 15;123(16):3061-3072. doi: 10.1002/cncr.30696. Epub 2017 Apr 14.

Immune responses and long-term disease recurrence status after telomerase-based dendritic cell immunotherapy in patients with acute myeloid leukemia.

Author information

1
Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia.
2
Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas.
3
Department of Hematology, The Ohio State University, Columbus, Ohio.
4
Department of Medicine, Loyola University, Maywood, Illinois.
5
Geron Corporation, Menlo Park, California.
6
Asterias Biotherapeutics Inc, Menlo Park, California.
7
Department of Oncology, Washington University School of Medicine, St. Louis, Missouri.

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 1×107 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.

KEYWORDS:

T cells; acute myeloid leukemia (AML); dendritic cells; human telomerase reverse transcriptase (hTERT); immunotherapy; recurrence-free survival; telomerase

PMID:
28411378
DOI:
10.1002/cncr.30696
[Indexed for MEDLINE]
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