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Long term disease-free survival and T cell and antibody responses in women with high-risk Her2+ breast cancer following vaccination against Her2.

Publication ,  Journal Article
Morse, MA; Hobeika, A; Osada, T; Niedzwiecki, D; Marcom, PK; Blackwell, KL; Anders, C; Devi, GR; Lyerly, HK; Clay, TM
Published in: J Transl Med
September 6, 2007

BACKGROUND: The HER2-inhibiting antibody trastuzumab, in combination with chemotherapy, significantly improves survival of women with resected, HER2-overexpressing breast cancers, but is associated with toxicities including a risk of cardiomyopathy. Additionally, the beneficial effect of trastuzumab is expected to decrease once the drug is discontinued. We proposed to address these concerns by using cancer vaccines to stimulate HER2 intracellular domain (ICD)-specific T cell and antibody responses. METHODS: Subjects with stage II (> or = 6 +LN), III, or stage IV breast cancer with > 50% HER2 overexpressing tumor cells who were disease-free after surgery and adjuvant therapy were eligible. Vaccines consisted of immature, cultured DC (n = 3), mature cultured DC (n = 3), or mature Flt3-ligand mobilized peripheral blood DC (n = 1) loaded with ICD, or tetanus toxoid, keyhole limpet hemocyanin or CMV peptide as controls, and were administered intradermally/subcutaneously four times at 3 week intervals. ICD-specific T cell and antibody responses were measured. Cardiac function was determined by MUGA or ECHO; long term disease status was obtained from patient contact. RESULTS: All seven patients successfully underwent DC generation and five received all 4 immunizations. There were no toxicities greater than grade 1 or ejection fraction decrements below normal. Delayed-type hypersensitivity (DTH) reactions at the injection site occurred in 6/7 patients and HER2 specificity was detected by cytokine flow cytometry or ELISPOT in 5 patients. At more than 5 years of follow-up, 6/7 had detectable anti-ICD antibodies. One patient experienced a pulmonary recurrence at 4 years from their study immunizations. This recurrence was resected and they are without evidence of disease. All patients are alive and disease-free at 4.6-6.7 years of follow-up. CONCLUSION: Although this was a small pilot study, the well-tolerated nature of the vaccines, the lack of cardiac toxicity, significant immunogenicity, and a 100% 4.5-year survival rate suggest that vaccination with HER2 ICD protein-containing DC is appropriate for further study in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT00005956.

Duke Scholars

Published In

J Transl Med

DOI

EISSN

1479-5876

Publication Date

September 6, 2007

Volume

5

Start / End Page

42

Location

England

Related Subject Headings

  • Vaccination
  • Time Factors
  • T-Lymphocytes
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Protein Structure, Tertiary
  • Middle Aged
  • Kaplan-Meier Estimate
  • Intracellular Space
  • Interferon-gamma
 

Citation

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Morse, M. A., Hobeika, A., Osada, T., Niedzwiecki, D., Marcom, P. K., Blackwell, K. L., … Clay, T. M. (2007). Long term disease-free survival and T cell and antibody responses in women with high-risk Her2+ breast cancer following vaccination against Her2. J Transl Med, 5, 42. https://doi.org/10.1186/1479-5876-5-42
Morse, Michael A., Amy Hobeika, Takuya Osada, Donna Niedzwiecki, Paul Kelly Marcom, Kimberly L. Blackwell, Carey Anders, Gayathri R. Devi, H Kim Lyerly, and Timothy M. Clay. “Long term disease-free survival and T cell and antibody responses in women with high-risk Her2+ breast cancer following vaccination against Her2.J Transl Med 5 (September 6, 2007): 42. https://doi.org/10.1186/1479-5876-5-42.
Morse MA, Hobeika A, Osada T, Niedzwiecki D, Marcom PK, Blackwell KL, et al. Long term disease-free survival and T cell and antibody responses in women with high-risk Her2+ breast cancer following vaccination against Her2. J Transl Med. 2007 Sep 6;5:42.
Morse, Michael A., et al. “Long term disease-free survival and T cell and antibody responses in women with high-risk Her2+ breast cancer following vaccination against Her2.J Transl Med, vol. 5, Sept. 2007, p. 42. Pubmed, doi:10.1186/1479-5876-5-42.
Morse MA, Hobeika A, Osada T, Niedzwiecki D, Marcom PK, Blackwell KL, Anders C, Devi GR, Lyerly HK, Clay TM. Long term disease-free survival and T cell and antibody responses in women with high-risk Her2+ breast cancer following vaccination against Her2. J Transl Med. 2007 Sep 6;5:42.
Journal cover image

Published In

J Transl Med

DOI

EISSN

1479-5876

Publication Date

September 6, 2007

Volume

5

Start / End Page

42

Location

England

Related Subject Headings

  • Vaccination
  • Time Factors
  • T-Lymphocytes
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Protein Structure, Tertiary
  • Middle Aged
  • Kaplan-Meier Estimate
  • Intracellular Space
  • Interferon-gamma