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Related Experiment Videos

HER2 dendritic cell vaccines.

Michael A Morse1, Timothy M Clay, Kirsten Colling

  • 1Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. morse004@mc.duke.edu

Clinical Breast Cancer
|March 7, 2003
PubMed
Summary
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Dendritic cell (DC) vaccines loaded with HER2 antigens are safe and feasible for breast cancer patients. While immune responses were modest, some patients showed no recurrence or stable disease, indicating potential for future HER2-targeted therapies.

Area of Science:

  • Immunology
  • Oncology
  • Vaccine Therapy

Background:

  • HER2/neu is overexpressed in approximately one-third of breast cancers, making it a target for vaccine therapies.
  • Dendritic cells (DCs) loaded with tumor antigens are a potent strategy for inducing T-cell responses.
  • Previous studies have explored HER2-targeted immunotherapies for breast and other HER2-expressing cancers.

Purpose of the Study:

  • To evaluate the safety, feasibility, and immunologic and clinical responses to HER2-loaded dendritic cell (DC) immunizations.
  • To assess responses in patients with high-risk resected breast cancer and metastatic HER2-expressing cancers.
  • To investigate the use of DCs loaded with either a HER2 peptide (E75) or HER2 intracellular domain (ICD) protein.

Main Methods:

  • Two small studies involving in vitro-generated DCs loaded with E75 peptide or ICD protein.

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  • Administration of loaded DCs to patients with advanced HER2/neu-expressing malignancies or high-risk breast cancer.
  • Assessment of safety (toxicities), feasibility, delayed-type hypersensitivity (DTH) reactions, T-cell responses (ELISPOT, proliferation), and clinical outcomes (stable disease, recurrence).

    • Main Results:

    • No toxicities were observed in any patients receiving HER2-loaded DC immunizations.
    • In metastatic cancer patients, 1 of 6 had stable disease for 6 months with E75-loaded DCs; others had progressive disease.
    • In high-risk breast cancer patients, all 3 receiving ICD-loaded DCs had no evidence of recurrence up to 2.5 years; T-cell responses were detected in 2 patients.

    Conclusions:

    • Generating and administering HER2-loaded DCs is feasible and safe for patients with advanced HER2/neu-expressing malignancies and high-risk breast cancer.
    • The immune responses generated by these HER2-loaded DC vaccines were modest.
    • More potent DC loading and maturation strategies are needed to optimize HER2-targeted vaccine efficacy.