Evaluation of therapeutic PD-1 antibodies by an advanced single-molecule imaging system for human PD-1 microclusters

Abstract

With recent advances in immune checkpoint inhibitors (ICIs), cancer immunotherapy has become the standard treatment for various malignant tumors. Their indications and dosages have been determined on the basis of several clinical trials conducted separately. In this study, we have established an advanced imaging system to visualize “human PD-1 microclusters,” in which PD-1 actually dephosphorylates both the TCR/CD3 complex and its downstream signaling molecules via the recruitment of a phosphatase, SHP2. Furthermore, each antibody required its own concentration and gained much greater effects in combination with other antibodies against different targets. We propose that our imaging system could digitally evaluate the PD-1-mediated T cell suppression and practical effects of each ICI. Currently, numerous new ICIs are tested, and more suitable combinations of them with other ICIs or conventional cancer treatments are being explored. Our study will have a wide range of applications to clinical practice in the future.

Engineering PD-1-targeted small protein variants for in vitro diagnostics and in vivo PET imaging

“…Consequently, the PD-1/PD-L1 pathway has emerged as a critical target for monoclonal antibodies-based inhibitors development targeting PD-1/ PD-L1 interaction. Such ICIs have demonstrated impressive activity against many cancers [10][11][12][13][14][15].…”