Antibody-Cytokine Fusion Proteins for the Therapy of Breast Cancer
Abstract
We have proposed to develop novel antibody fusion proteins in which antibodies specific for the breast cancer tumor associated antigen HER2/neu will be genetically fused to the cytokines IL-2, IL-12, and GM-CSF. It is expected that the anti-HER2/neu antibody cytokine fusion protein will localize the cytokine at the tumor and elicit an immune response. During our first year of funding we completed the construction and characterization of an anti-HER2/neu IgG3-(GM-CSF) fusion protein. This novel molecule expressed in myeloma cells was correctly assembled and secreted and showed antibody and cytokine related activities. In addition, anti-HER2/neu IgG3-(GM-CSF) was able to target the HER2/neu expressing murine tumor CT26-HER2/neu and enhance the immune response against the targeted antigen, HER2/neu, suggesting its potential use in the treatment of HER2/neu expressing tumors. We also expanded our repertoire of human HER2/neu expressing murine cell lines by transducing the murine B cell lymphoma 38C13 with the cDNA encoding human HER2/neu. We studied the in vivo properties of this new tumor model (38C13-HER2/neu) and found that this model provides a useful tool for the evaluation of different therapeutic approaches designed to stimulate the tumor specific immune response.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA385807
Entities
People
- Sherri Morrison
Organizations
- University of California, Los Angeles