Accession Number:

ADA443713

Title:

Fusions of Breast Carcinoma and Dendritic Cells as a Vaccine for the Treatment of Metastatic Breast Cancer

Descriptive Note:

Annual rept. 1 Jul 2004-30 Jun 2005

Corporate Author:

DANA-FARBER CANCER INST BOSTON MA

Personal Author(s):

Report Date:

2005-07-01

Pagination or Media Count:

24.0

Abstract:

The overall objective of the project is to study the safety, immunologic response, and clinical effect of vaccination with the dendritic cell DCtumor fusions in conjunction with IL-12 in patients with breast cancer. The hypothesis underlying the proposed study is that fusions generated with patient-derived breast carcinoma cells and autologous DC will stimulate a broad anti-tumor response that will be further augmented by the presence of IL-12. In the first phase of the project, we have conducted pre-clinical investigations to further define the biology and enhance the efficacy of the fusion cell vaccine. During this period, we have also been completing DOD mandated regulatory requirements in order to initiate the planned clinical trial. In the first year of the project, we sought to define the optimal DC population to enhance vaccine efficacy. We examined the impact of DC maturation on the immunologic potency of the fusion vaccine. We demonstrated that polyethylene glycol PEG-mediated fusion results in maturation and activation of the DC fusion partner. Mature DCtumor fusions exhibited prominent levels of expression of costimulatory molecules, IL-I 2, and chemokine receptors necessary for migration to draining lymph nodes. Based on these findings, we elected to use DCs matured with TNFa to generate fusion cells for the clinical trial.

Subject Categories:

  • Biochemistry
  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE