Cancer-targeted T cell Receptors - the next generation immunotherapeutic drugs

The aim is to generate recombinant T cell receptors (TcRs) that recognize cancer cells. DNA encoding the receptors forms basis for novel drugs for immunotherapy of cancer. Two strategies are followed to select T cells with the desired receptors: 1) T cell s that recognize common cancer proteins, such as telomerase, have been isolated from patients successfully treated by peptide vaccination. A large number of clones that kill tumor cells selectively and efficiently have been isolated. Telomerase is overexp ressed in 90% of cancers. The TcRs can therefore be widely applied. 2) An innovative strategy has been developed to select T cells that kill specific cell types independently of tumor-associated antigens. Tissue-restricted cytotoxicity is a rational treat ment option when cancer occurs in tissues that are not essential for the host, or can be replaced by transplantation. Cell type-specific T cells are generated by exposing normal T cells to a foreign HLA molecule with a peptide from a cell type-restricted protein. Fluorescent HLA-peptide complexes are used to detect and isolate the specific cells. The strategy allows immunization against a large number of molecules for more efficient immunotherapy. Methods for selecting and cloning T cells with desired rea ctivity are used in combination with state of the art technology for isolating and amplifying DNA encoding TcRs. Continued identification of cell type-restricted peptides will be performed by bioinformatics and DNA microarray technologies. The applicants, Olweus and Gaudernack, will collaborate with several FUGE platforms, leading intenational experts and industry to optimize the components needed to translate the results into clinical practise. The research is conducted in an environment actively involve d in several clinical trials for cancer immunotherapy, and with a strong record in translational research. The project applied for is planned to enter phase I clinical trials by end of 2009.