New Strategy for the Redirection of Cytolytic T Lymphocytes to Breast Tumors
Abstract
The main objective of this research project has been to apply the T-body approach for the immunotherapy of breast cancer. To this end we have altered the specificity of patient-derived lymphocytes through stable modification with chimeric receptor genes consisting of either an anti-breast tumor single-chain variable (scFv) region of anti- HER2 antibody or the Erb-B NDF ligand linked to a T cell activation molecule (the gamma subunit of the Fc epsilon receptor) Both receptors recognize molecules specifically overexpressed on many breast tumors. A special receptor configuration developed and tested in this study included part of the extracellular and the entire intracellular domains of the co- stimulatory CD2B molecule in-between the scFv and the gamma moieties of the chimeric receptors. This three partied receptor appeared functional in redirecting hybridoma cell lines, human PBLs and resting lymphocytes of transgenic mice. Such genetically modified redirected lymphocytes will be tested on explanted breast tumor cells for specific lysis and secretion of cytokines in vitro, and for elimination of human breast tumor cells passaged in NOD/SCID mice in vivo. These model systems will serve to determine the optimal conditions towards clinical trials. Altogether, this therapeutic strategy may allow new approaches towards the adoptive immunotherapy of breast cancer in humans.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADA387650
Entities
People
- Zelig Eshhar
Organizations
- Weizmann Institute of Science