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Immune responses and long‐term disease recurrence status after telomerase‐based dendritic cell immunotherapy in patients with acute myeloid leukemia
Author(s) -
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.
Publication year - 2017
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.30696
Subject(s) - medicine , telomerase reverse transcriptase , myeloid leukemia , immunology , leukapheresis , telomerase , myeloid , immunotherapy , antigen , immune system , oncology , gastroenterology , stem cell , cd34 , biochemistry , chemistry , genetics , gene , biology
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 .