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

Hanna J. Khoury, Robert H. Collins, William Blum, Patrick S. Stiff, Laurence Elias, Jane S. Lebkowski, Anita Reddy, Kevin P. Nishimoto, Debasish Sen, Edward D. Wirth, Casey C. Case, John F. DiPersio

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27 Scopus citations

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.

Original languageEnglish
Pages (from-to)3061-3072
Number of pages12
JournalCancer
Volume123
Issue number16
DOIs
StatePublished - Aug 15 2017

Keywords

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

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    Khoury, H. J., Collins, R. H., Blum, W., Stiff, P. S., Elias, L., Lebkowski, J. S., Reddy, A., Nishimoto, K. P., Sen, D., Wirth, E. D., Case, C. C., & DiPersio, J. F. (2017). Immune responses and long-term disease recurrence status after telomerase-based dendritic cell immunotherapy in patients with acute myeloid leukemia. Cancer, 123(16), 3061-3072. https://doi.org/10.1002/cncr.30696