RRC ID 72442
Author Wataru Nishi, Ei Wakamatsu, Hiroaki Machiyama, Ryohei Matsushima, Kensho Saito, Yosuke Yoshida, Tetsushi Nishikawa, Tomohiro Takehara, Hiroko Toyota, Masae Furuhata, Hitoshi Nishijima, Arata Takeuchi, Miyuki Azuma, Makoto Suzuki, Tadashi Yokosuka
Title 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.
DOI 10.21203/rs.3.rs-1945681/v1
PMID 37280233
PMC PMC10244369
MeSH B7-H1 Antigen / metabolism Humans Immunotherapy / methods Neoplasms* / diagnostic imaging Neoplasms* / drug therapy Nivolumab / pharmacology Nivolumab / therapeutic use Programmed Cell Death 1 Receptor* Receptors, Antigen, T-Cell Single Molecule Imaging
Mice RBRC02142