TAP-inhibitors from old world primate 1-herpesviruses and their use: WO2009008713

Abstract

Cytotoxic T lymphocytes (CTLs) recognize peptide antigens in the context of major histocompatibility complex (MHC) class I molecules. CTL-mediated immunity is important for defense against cancers and virus infections, and thus viruses and tumors have evolved CTL-evasion mechanisms. The transporter associated with antigen processing (TAP) is a key factor for MHC class I assembly, and TAP is a frequent target of immune evasion by viruses and tumors. WO2009008713 discloses potential therapeutic uses of TAP inhibitors encoded by Epstein–Barr virus and its lymphocryptovirus (LCV) homologs. In particular, WO2009008713 proposes the use of LCV TAP inhibitors and their combinations with other viral TAP inhibitors to elicit novel categories of CTLs that destroy target cells in which the function of TAP or other components of the MHC class I assembly pathway is inhibited. Alternatively, WO2009008713 proposes the use of LCV TAP inhibitors and their combinations with other viral TAP inhibitors to more efficiently generate tumor-specific T-cell epitopes for immunotherapy. The methods described in WO2009008713 offer the promise of new strategies of cancer immunotherapy. However, significant optimization of therapy conditions and characterizations of eligible tumor types will be needed to further develop therapeutic use of TAP inhibitors.