Abstract
A phase I clinical trial was conducted to assess safety, tolerability and preliminary efficacy of a heterologous prime-boost strategy, involving a plasmid DNA (pHM-GM-CSF, expressing truncated HER2 and GM-CSF as a bicistronic message) and an adenoviral vector (Ad-HM, containing the same modified HER2 sequence only), in subjects with stage III-IV metastatic breast cancer expressing HER2 (1+∼3+ by immunohistochemistry). Nine eligible subjects were divided into three cohorts based on three different DNA doses (2, 4 and 8 mg) of pHM-GM-CSF, which were intramuscularly injected three times on weeks 0, 2, and 4 (i.e. 6, 12, and 24mg in total), followed by a single injection of Ad-HM (3x109 viral particle) on week 6. Relevant parameters were measured during the 6-month follow-up period. Seven minor grade 1 toxicities were found in four of nine patients, while no drug-related serious adverse event was reported. HER2-specific cell-mediated or humoral immunities were produced in all (100 %) or three patients (33 %), respectively. One patient showed a partial response, and seven subjects had stable diseases. No clear correlation was observed between DNA dosages and induction of immunogenicity and clinical tumor response. Our data showed that intramuscular injection of pHM-GM-CSF 24mg and Ad-HM 3x109 VP were well tolerated and safe. To our knowledge, this is the first clinical study demonstrating an efficient induction of HER2-specific cellular and humoral responses in patients with metastatic breast cancer expressing HER2.
Citation Format: SUNGBAE KIM, KyungHae Jung, JinHee Ahn, Jeongeun Kim. Efficient induction of cellular and humoral immune responses by heterologous prime-boost therapeutic vaccination, involving plasmid DNA and adenoviral vector, in subjects with HER2-expressing breast cancer: Results from a phase Ib study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT414. doi:10.1158/1538-7445.AM2014-CT414
- ©2014 American Association for Cancer Research.
Volume 74, Issue 19 Supplement
