New Strategy for the Redirection of Cytolytic T Lymphocytes to Prostate Tumors
Abstract
Our group has developed a model immunotherapy system using a chimeric T cell receptors to redirect cytotoxic T cells to tumors. The efficacy of this approach in reducing tumor burden has been demonstrated using our constructs in models of ovarian carcinoma. To apply this technology to prostate tumors, we will alter the specificity of patient-derived lymphocytes through stable modification with chimeric receptor genes consisting of a targeting molecule linked to a T cell activation molecule (the y subunit common to the Fc receptors, CD28 co-stimulatory receptor or Syk kinase). We have cloned, expressed, and immunized mice with two antigens expressed specifically on a large proportion of prostate tumors. These immunized mice will be used to produce prostate-specific monoclonal antibodies from which the scFv will be prepared. In addition, we have produced retroviruses capable of transducing human PBL with a chimeric receptor gene. Three targeting molecules have been used. We demonstrated their efficacy and the ability of the transduced lymphocytes to kill a prostate carcinoma line, LNCaP. We have started to put these constructs into lentiviral vectors which have the ability to transduce non- replicating cells. This therapeutic strategy may allow new approaches towards the adoptive immunotherapy of prostate cancer in humans.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1999
- Accession Number
- ADA385982
Entities
People
- Zelig Eshhar
Organizations
- Weizmann Institute of Science