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

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish (US)
JournalCancer
DOIs
StateAccepted/In press - 2017

Fingerprint

Telomerase
Acute Myeloid Leukemia
Immunotherapy
Dendritic Cells
Recurrence
Vaccination
human TERT protein
Leukapheresis
Injections
Idiopathic Thrombocytopenic Purpura
HLA Antigens

Keywords

  • Acute myeloid leukemia (AML)
  • Dendritic cells
  • Human telomerase reverse transcriptase (hTERT)
  • Immunotherapy
  • Recurrence-free survival
  • T cells
  • Telomerase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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

In: Cancer, 2017.

Research output: Contribution to journalArticle

Khoury, HJ, Collins, RH, Blum, W, Stiff, PS, Elias, L, Lebkowski, JS, Reddy, A, Nishimoto, KP, Sen, D, Wirth, ED, Case, CC & Dipersio, JF 2017, 'Immune responses and long-term disease recurrence status after telomerase-based dendritic cell immunotherapy in patients with acute myeloid leukemia', Cancer. https://doi.org/10.1002/cncr.30696
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. / Immune responses and long-term disease recurrence status after telomerase-based dendritic cell immunotherapy in patients with acute myeloid leukemia. In: Cancer. 2017.
@article{e02d216641ca42a195c520d739f53ba8,
title = "Immune responses and long-term disease recurrence status after telomerase-based dendritic cell immunotherapy in patients with acute myeloid leukemia",
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.",
keywords = "Acute myeloid leukemia (AML), Dendritic cells, Human telomerase reverse transcriptase (hTERT), Immunotherapy, Recurrence-free survival, T cells, Telomerase",
author = "Khoury, {Hanna J.} and Collins, {Robert H.} and William Blum and Stiff, {Patrick S.} and Laurence Elias and Lebkowski, {Jane S.} and Anita Reddy and Nishimoto, {Kevin P.} and Debasish Sen and Wirth, {Edward D.} and Case, {Casey C.} and Dipersio, {John F.}",
year = "2017",
doi = "10.1002/cncr.30696",
language = "English (US)",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",

}

TY - JOUR

T1 - Immune responses and long-term disease recurrence status after telomerase-based dendritic cell immunotherapy in patients with acute myeloid leukemia

AU - Khoury, Hanna J.

AU - Collins, Robert H.

AU - Blum, William

AU - Stiff, Patrick S.

AU - Elias, Laurence

AU - Lebkowski, Jane S.

AU - Reddy, Anita

AU - Nishimoto, Kevin P.

AU - Sen, Debasish

AU - Wirth, Edward D.

AU - Case, Casey C.

AU - Dipersio, John F.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Acute myeloid leukemia (AML)

KW - Dendritic cells

KW - Human telomerase reverse transcriptase (hTERT)

KW - Immunotherapy

KW - Recurrence-free survival

KW - T cells

KW - Telomerase

UR - http://www.scopus.com/inward/record.url?scp=85017551412&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85017551412&partnerID=8YFLogxK

U2 - 10.1002/cncr.30696

DO - 10.1002/cncr.30696

M3 - Article

C2 - 28411378

AN - SCOPUS:85017551412

JO - Cancer

JF - Cancer

SN - 0008-543X

ER -