Efficacy of dual checkpoint-blockade in solid tumors, part 1

Checkpoint inhibition is one of the most important medical discoveries of the 21st century. Not without reason James P. Allison and Tasuku Honjo received the Nobel Prize in medicine 2018 for their work in this field. The idea to fight cancer by activating immune response, e.g., by cytokines or IL‑2, has been around for decades with limited success. In contrast to these unspecific approaches, the idea of checkpoint inhibition (CPI) is to enhance T‑cell activation, leading to tumor elimination. Apart from CPI monotherapy, there is evidence for synergistic efficacy of combination strategies using inhibitors of the PD-L1/PD‑1 axis plus CTLA4, LAG3, and TIGIT, respectively. There is, however, quite variable efficacy of these combinations across many solid tumor entities, which might be due to differences in tumor heterogeneity and resistance mechanisms. …