Recent Progress of Potentiating Immune Checkpoint Blockade with External Stimuli-an Industry Perspective

The past decade has seen the materialization of immune checkpoint blockade as an emerging approach to cancer treatment. However, the overall response and patient survival are still modest. Various efforts to study the cancer immunogram have highlighted complex biology that necessitates a multipronged approach. This includes increasing the antigenicity of the tumor, strengthening the immune infiltration in the tumor microenvironment, removing the immunosuppressive mechanisms, and reducing immune cell exhaustion. The coordination of these approaches, as well as the ability to enhance them through delivery, is evaluated. Due to their success in multiple preclinical models, external-stimuli-responsive nanoparticles have received tremendous attention. Several studies report success in distantly located tumor regression, metastases, and reoccurrence in preclinical mouse models. However, clinical translation in this space remains low. Herein, the recent advancement in external-stimuli-responsive nanoconstruct-synergized immune checkpoint blockade is summarized, offering an industry perspective on the limitations of current academic innovations and discussing challenges in translation from a technical, manufacturing, and regulatory perspective. These limitations and challenges will need to be addressed to establish external-stimuli-based therapeutic strategies for patients.