Immune responses and long‐term disease recurrence status after telomerase‐based dendritic cell immunotherapy in patients with acute myeloid leukemia
Open accessAbstract
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.
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mRNA vaccines have shown good efficacy in the treatment of acute myelocytic leukemia (AML), non-small cell lung cancer (NSCLC), and melanoma.
“mRNA vaccines have shown good efficacy in the treatment of acute myelocytic leukemia (AML),339–341 non-small cell lung cancer (NSCLC),342,343 and melanoma344–348 (Table 3).”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [341]
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- Authors
- 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.
- Affiliations
- Emory University (US)
- The University of Texas Southwestern Medical Center (US)
- The Ohio State University (US)
- Loyola University Medical Center (US)
- Geron (United States) (US)
- Asterias Biotherapeutics Inc Menlo Park California
- Washington University in St. Louis (US)
- Corresponding author
- Lebkowski, Jane S.
- ORCID
- Venue
- Cancer
- Publisher
- Wiley
- Published
- 2017-04-14
- Volume
- 123
- Issue
- 16
- Pages
- 3061-3072
- ISSN
- 0008-543X (ISSN-L)
- 1097-0142
- OpenAlex
- W2606935378
- Cited by
- 102
- References
- 50
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 9 · 2023: 8 · 2022: 9 · 2021: 19 · 2020: 14 · 2019: 12 · 2018: 7 · 2017: 3
- FWCI
- 4.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- acute myeloid leukemia, dendritic cell immunotherapy, telomerase reverse transcriptase, hTERT, autologous dendritic cells, mRNA electroporation, lysosomal targeting, intradermal vaccination, recurrence, recurrence-free survival, immunogenicity, immunotherapy safety, high-risk AML, complete remission
- MeSH terms
- Adult, Aged, Dendritic Cells, Feasibility Studies, Female, Humans, Immunotherapy, Leukapheresis, Male, Middle Aged, Remission Induction, RNA, Messenger, T-Lymphocytes, Leukemia, Myeloid, Acute, Disease-Free Survival, Telomerase, Cancer Vaccines, Enzyme-Linked Immunospot Assay
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