University of Michigan Medical School, Department of Microbiology and Immunology, 5641 Medical Science Building II, Ann Arbor, MI 48109-5620, USA.
Expert Opin Ther Pat. 2010 Feb;20(2):277-82. doi: 10.1517/13543770903501563.
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.
细胞毒性 T 淋巴细胞 (CTL) 通过主要组织相容性复合体 (MHC) I 类分子识别肽抗原。CTL 介导的免疫对于防御癌症和病毒感染很重要，因此病毒和肿瘤已经进化出 CTL 逃逸机制。抗原加工相关转运蛋白 (TAP) 是 MHC I 类组装的关键因素，TAP 是病毒和肿瘤免疫逃逸的常见靶点。WO2009008713 公开了 Epstein-Barr 病毒及其淋巴隐病毒 (LCV) 同源物编码的 TAP 抑制剂的潜在治疗用途。特别是，WO2009008713 提出了使用 LCV TAP 抑制剂及其与其他病毒 TAP 抑制剂的组合，以引发新类别的 CTL，破坏 TAP 或 MHC I 组装途径其他成分的功能受到抑制的靶细胞。或者，WO2009008713 提出使用 LCV TAP 抑制剂及其与其他病毒 TAP 抑制剂的组合，以更有效地产生用于免疫治疗的肿瘤特异性 T 细胞表位。WO2009008713 中描述的方法为癌症免疫治疗提供了新策略的希望。然而，需要对治疗条件进行重大优化，并对合格的肿瘤类型进行特征描述，以进一步开发 TAP 抑制剂的治疗用途。
