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Breast Cancer Vaccines Based on Dendritic Cells and the Chemokines

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Annual rept. 1 Jul 1997-30 Jun 1998

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The major objective of this project is to establish a new modality for the treatment of breast cancer that employs the combination of chemokine gene-modified fibroblasts with breast tumor-pulsed dendritic cells DC to both recruit andor concentrate from the periphery low frequency immune reactive T cells as well as to potently stimulate these effector cells once localized at the vaccination site. During the second year of this four-year project, studies were focused on three major areas either specified in the Statement of Work or in response to issues raised in the original Peer Review Panel Report 1 to complete in vitro optimization of human DC generation and function 2 to obtain high level chemokine cDNA expression in autologous breast cancer fibroblasts and 3 to establish a relevant breast tumor model in mice to test effective vaccine strategies based on dendritic cells and chemokines. The first and third areas have been highly successful and have to date resulted in three 3 publications. We have also made new progress in the second area we have moved away from retroviral supernatant transduction to particle-mediated gene gun or biolistics gene transfer to obtain more reliable and higher levels of chemokine production by fibroblasts. Lastly, we have altered our original proposed plan of attack and provide alternative new approaches for Technical Objectives 1 and 3 as a result of certain unforeseen limitations in obtaining adequate tumor and blood samples from breast cancer patients, which are detailed. Collectively, the data and appended publications provided in this second annual report demonstrate steady progress and productivity toward meeting the overall goal of the funded research.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

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