New Strategy for the Redirection of Cytolytic T Lymphocytes to Prostate Tumors
Abstract
We developed an immunotherapy system using chimeric T cell receptors to redirect T cells to tumors. The objective of this research project has been to study the ability of effector lymphocytes expressing chimeric receptors (CR) to eliminate prostate cancer (PC). Previously we showed that such T cells can kill target PC cells in vitro. Now we report on successful attempts to reject PC xenografts in vivo in SCID mice. Retrovectors harboring HER2-specific CR genes where the scFv is linked to CD28 and the FcR gamma are used to efficiently transduce activated human lymphocytes. When injected into the CWR22 PC xenograft, about 30% of mice treated with the anti-HER2 (and not control anti-TNP), a complete tumor rejection was observed, evident by disappearance of tumor concurrently with a decrease in PSA levels. In several of the treated mice where the xenograft growth was resumed, we found that the re-growing tumor cells lost their ability to bind the particular anti-HER2 antibody that served to construct the CR. These cells could stilt bind to an antibody directed to another HER2 epitope. IL-2 was found to be required for more efficient cancer rejection. This therapeutic strategy may allow new approach towards the adoptive immunotherapy of localized PC.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2001
- Accession Number
- ADA392363
Entities
People
- Zelig Eshhar
Organizations
- Weizmann Institute of Science