Enhanced Eradication of Lymphoma by Tumor-Specific Cytotoxic T Cells Secreting an Engineered Tumor-Specific Immunotoxin
Abstract
In this project we propose to use tumor-specific T cells to produce an immunotoxin (IT) targeting tumor cells only when these T cells are specifically activated by the tumor. We use lentiviral vectors to modify tumor specific T cells with our immunotoxin. PEA based immunotoxins affect cell viability by ADP ribozilation of their elongation factor-2. To produce high titer of vector encoding the IT we needed to generate a producer cell line resistant to PEA toxin. Several methods including the use of two mutated elongation factors drug and peptides blocking PEA effect were used to protect the producer cells from the lethal activity of the toxin thus increasing the production of proteins by these cells. We have established stable cell lines of PEA-resistant producer cells and showed that cells protected against PEA produced a significant higher amount of IT. Using these stable cell lines we will produce a high titer of IT-lentivirus preparation. We have also generated vectors encoding survival genes to further protect the producer cells as well as the IT-modified tumor-specific T cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2008
- Accession Number
- ADA487516
Entities
People
- Yotnda Patricia
Organizations
- Baylor College of Medicine