A phase 1 study of a heterologous prime-boost vaccination involving a truncated HER2 sequence in patients with HER2-expressing breast cancer
A phase 1 clinical trial was conducted to assess the safety, tolerability, and preliminary efficacy of a heterologous prime-boost strategy involving plasmid DNA (pHM-GM-CSF, expressing truncated human epidermal growth factor receptor 2 (HER2) and granulocyte macrophage colony-stimulation factor (GM-...
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doaj-de1a57c2423e45828860b873d5d9b86e2020-11-25T02:06:08ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012015-01-012A phase 1 study of a heterologous prime-boost vaccination involving a truncated HER2 sequence in patients with HER2-expressing breast cancerSung-Bae Kim0Jin-Hee Ahn1Jeongeun Kim2Kyung Hae Jung3Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Songpa-Gu, Seoul, KoreaDepartment of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Songpa-Gu, Seoul, KoreaDepartment of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Songpa-Gu, Seoul, KoreaDepartment of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Songpa-Gu, Seoul, KoreaA phase 1 clinical trial was conducted to assess the safety, tolerability, and preliminary efficacy of a heterologous prime-boost strategy involving plasmid DNA (pHM-GM-CSF, expressing truncated human epidermal growth factor receptor 2 (HER2) and granulocyte macrophage colony-stimulation factor (GM-CSF) as a bicistronic message) and an adenoviral vector (Ad-HM, containing the same modified HER2 sequence only), in patients with stage IIIâIV metastatic breast cancer expressing HER2. Nine eligible subjects were divided into three cohorts based on the dosages (2, 4, and 8 mg/patient/visit) of pHM-GM-CSF used as the primer, which was intramuscularly injected three times at weeks 0, 2, and 4. It was followed by a single injection of Ad-HM (3 Ã 109 virus particles), used as a booster, at week 6. During the 6-month follow-up period, adverse events (AEs), pharmacokinetics and pharmacodynamics, and HER2-specific cellular and humoral immune responses were evaluated. Seven cases of minor grade 1 toxicities in four of nine subjects and no serious drug-related AEs were reported. HER2-specific cell-mediated or humoral immunity was produced in all (100%) or three subjects (33%), respectively. One subject showed a partial response, and seven subjects had stable diseases. However, there were no differences in clinical tumor response and HER2-specific immune responses among the cohorts. These results showed that intramuscular injections of pHM-GM-CSF and Ad-HM were well tolerated and safe.http://www.sciencedirect.com/science/article/pii/S2329050116300432 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sung-Bae Kim Jin-Hee Ahn Jeongeun Kim Kyung Hae Jung |
spellingShingle |
Sung-Bae Kim Jin-Hee Ahn Jeongeun Kim Kyung Hae Jung A phase 1 study of a heterologous prime-boost vaccination involving a truncated HER2 sequence in patients with HER2-expressing breast cancer Molecular Therapy: Methods & Clinical Development |
author_facet |
Sung-Bae Kim Jin-Hee Ahn Jeongeun Kim Kyung Hae Jung |
author_sort |
Sung-Bae Kim |
title |
A phase 1 study of a heterologous prime-boost vaccination involving a truncated HER2 sequence in patients with HER2-expressing breast cancer |
title_short |
A phase 1 study of a heterologous prime-boost vaccination involving a truncated HER2 sequence in patients with HER2-expressing breast cancer |
title_full |
A phase 1 study of a heterologous prime-boost vaccination involving a truncated HER2 sequence in patients with HER2-expressing breast cancer |
title_fullStr |
A phase 1 study of a heterologous prime-boost vaccination involving a truncated HER2 sequence in patients with HER2-expressing breast cancer |
title_full_unstemmed |
A phase 1 study of a heterologous prime-boost vaccination involving a truncated HER2 sequence in patients with HER2-expressing breast cancer |
title_sort |
phase 1 study of a heterologous prime-boost vaccination involving a truncated her2 sequence in patients with her2-expressing breast cancer |
publisher |
Elsevier |
series |
Molecular Therapy: Methods & Clinical Development |
issn |
2329-0501 |
publishDate |
2015-01-01 |
description |
A phase 1 clinical trial was conducted to assess the safety, tolerability, and preliminary efficacy of a heterologous prime-boost strategy involving plasmid DNA (pHM-GM-CSF, expressing truncated human epidermal growth factor receptor 2 (HER2) and granulocyte macrophage colony-stimulation factor (GM-CSF) as a bicistronic message) and an adenoviral vector (Ad-HM, containing the same modified HER2 sequence only), in patients with stage IIIâIV metastatic breast cancer expressing HER2. Nine eligible subjects were divided into three cohorts based on the dosages (2, 4, and 8 mg/patient/visit) of pHM-GM-CSF used as the primer, which was intramuscularly injected three times at weeks 0, 2, and 4. It was followed by a single injection of Ad-HM (3 Ã 109 virus particles), used as a booster, at week 6. During the 6-month follow-up period, adverse events (AEs), pharmacokinetics and pharmacodynamics, and HER2-specific cellular and humoral immune responses were evaluated. Seven cases of minor grade 1 toxicities in four of nine subjects and no serious drug-related AEs were reported. HER2-specific cell-mediated or humoral immunity was produced in all (100%) or three subjects (33%), respectively. One subject showed a partial response, and seven subjects had stable diseases. However, there were no differences in clinical tumor response and HER2-specific immune responses among the cohorts. These results showed that intramuscular injections of pHM-GM-CSF and Ad-HM were well tolerated and safe. |
url |
http://www.sciencedirect.com/science/article/pii/S2329050116300432 |
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