Transfer of T Cell Specificity for the Treatment of Breast Cancer: A Preclinical Study
Abstract
Overexpression of Her-2/neu is one of the major alterations in breast cancer and is associated with metastatic disease, poor prognosis and overall survival. Her-2/neu is a self antigen, therefore, self-tolerance is a major burden for the induction of effective antitumor immune responses. Clinical trials show that immunizations with neu-antigens do not promote a potent protective mediated immune response. In order to develop a therapy to target Her-2/neu expressing tumors, we have devised a strategy where we can endow T cells with antitumor specificity and bypass the effect of self-tolerance. We developed an approach by genetic engineering where we have genetically altered T cell populations to express high affinity T cell receptors (TCR) chains specific for Her-2/neu. High affinity TCR were obtained from A2.1 transgenic mice immunized with A2. 1 -Her-2/neu immunodominant epitopes. The TCR genes from the CTLs were cloned and engineered to be expressed on T cells. T cells expressing these engineered TCR can recognize and kill Her-2/neu expressing breast tumors. These results demonstrate a novel strategy to target Her-2/neu positive tumors for the treatment of breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA407487
Entities
People
- Daniel P. Gold
- Joseph Lustgarten