Approaches to overcome the current treatment plateau in immunotherapy

After its practice-changing success, immune checkpoint inhibitors (ICI) have possibly reached a treatment plateau and novel drug candidates are currently being investigated to overcome resistance to ICI including patients who never responded to ICI. With some of the recent failures of novel checkpoint inhibitors, there has been a shift of focus to other modalities such as antibody drug conjugates and radiopharmaceuticals. And skepticism towards novel agents in immunotherapy, including cell therapies, has yet to be replaced by renewed optimism. The combination of ICI with anti-angiogenic agents appeared as a promising new approach to avoid or revert resistance to ICI. Following these encouraging observations, bispecific agents have followed suit and are emerging as possible advancements. Targeting other immune cells, such as macrophages and epigenetic modulation hold additional promise to overcome resistance. Finally, the recent progress in vaccine development may provide a novel approach to selectively activate the global immune system and re-direct its components to reject tumors. Overall, it appears that the full potential of immunomodulators has not yet been fully achieved. Thus, improving the understanding of cancer biology, the interaction with the immune system and identifying patient subsets who might benefit from resetting their immune system continue to be opportunities for oncology drug development.