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

The aim is to generate recombinant T cell receptors that recognize cancer cells. DNA encoding the receptors form basis for novel drugs for immunotherapy of cancer. Two strategies are followed to select T cells with the desired receptors: 1) A large number of T cell clones recognizing common cancer proteins, such as telomerase, have been isolated from patients successfully treated by peptide vaccination. These clones kill tumor cells selectively and efficiently. Telomerase is overexpressed in 90% of cancer s. 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 treatment 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 HL A-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. A number of cell-type specific T cell lines have been successfully generated. Met hods for cloning of these T cells will be 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, mass spectrometry and DNA microarray technologies. The applicant, Olweus, and partner Gaudernack, will collaborate with leading international experts and industry to optimize the components needed to translate the results into clinical practice. The research is conducted in an environment actively involved in several clinical trials for cancer immunotherapy, and with a strong record in translational research. The project applied for is planned to enter clinical trials by end of 2010