Anti-HER2/Toxin Expressing Lymphocytes for Breast Cancer Therapy
Abstract
Development of immunotherapy and gene therapy with the ability to selectively destroy tumor cells is an important goal for future breast cancer therapy. Recently in our lab, a new class of breast cancer killer cells was designed and generated by modifying lymphocytes to produce an anti-HER-2 directed toxin. A single chain antibody with high-affinity binding to the extra cellular domain of HER-2 was fused with a truncated Pseudomonas exotoxins A gene. The transduced lymphocytes were shown to specifically kill breast cancer cells overexpressing this tumor antigen both in vitro and in a nude mouse model. The purpose of the current study is to modify and improve this novel anti-HER-2/toxin-expressing cell strategy for breast cancer therapy. Toward this goal, an efficient gene transfer system has been developed and the biological properties of the transduced lymphocytes assessed. Cytokines, such as interleukin-2 and granulocyte-macrophage colony stimulating factor, have been incorporated into the toxin expression cassette using an internal ribosome entry site in order to enhance anti-tumor activity of the transduced lymphocytes. We will attempt to increase tumor homing of the transduced lymphocytes by co-expressing cytokines and incorporate an inducible suicide mechanism for safety. This study should set the foundation for translating this novel approach for breast cancer therapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 1999
- Accession Number
- ADA381281
Entities
People
- Jenny H. Hester
Organizations
- Wake Forest University