In some embodiments, the methods involve the use of a combination of at least two of the following: an inhibitor of indoleamine-2,3-dioxygenase (IDO), an inhibitor of the PD-L1/PD-1 pathway, an inhibitor of CTLA-4, an inhibitor of CD25, or IL-7. The inventors particularly observed a major synergistic effect of combining anti-CTLA-4 with either an IDO inhibitor, with anti-PD-L1 mAb, or with CD-25 depletion. Such combinations have been found to demonstrate a synergistic effect in treating cancer and tumors, for example by reducing tumor size, increasing the percentage of antigen-specific T cells, and increasing T cell function.
在一些实施方式中,这些方法涉及至少两种以下物质的组合使用:缓解
吲哚胺-2,3-二氧化酶(
IDO)的
抑制剂、PD-L1/PD-1通路的
抑制剂、CT
LA-4的
抑制剂、CD25的
抑制剂或IL-7。发明者特别观察到将抗CT
LA-4与
IDO抑制剂、抗PD-L1单抗或CD-25耗尽结合的主要协同作用。这些组合已被发现在治疗癌症和肿瘤中展现出协同作用,例如通过减小肿瘤大小、增加特异性抗原T细胞的百分比以及增强T细胞功能。