Enhanced Eradication of Lymphoma by Tumor-Specific Cytotoxic T Cells Secreting and Engineered Tumor-Specific Immunotoxin
Annual rept. 15 May 2008-14 May 2009
BAYLOR COLL OF MEDICINE HOUSTON TX
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In this project, we proposed 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 generated a producer cell line resistant to PEA toxin. We have established stable cell lines of PEA- resistant producer cells. Using these stable cell lines, we have produced a high titer of IT-lentivirus preparation and transduced T cells with these vectors encoding the immunotoxin. We have characterized the transduced T cells to ensure that their phenotype and function was not impaired by the genetic modification and compared them to parental T cells. Finally, we have verified that transduced T cells produced the therapeutic immunotoxin that specifically kills our targeted tumor cells.
- Medicine and Medical Research