Granzyme B nanoreporter for early monitoring of tumor response to immunotherapy
Menée in vitro et à l'aide de modèles murins de tumeurs, cette étude met en évidence l'intérêt, pour évaluer la réponse tumorale à une immunothérapie, d'une nanomolécule combinant un anti-PD-L1 et un système de sonde sensible aux granzymes B libérés par les lymphocytes T
Despite recent advancements in cancer immunotherapy, accurate monitoring of its efficacy is challenging due to heterogeneous immune responses. Conventional imaging techniques lack the sensitivity and specificity for early response assessment. In this study, we designed a granzyme B (GrB) nanoreporter (GNR) that can deliver an immune checkpoint inhibitor to the tumor and track time-sensitive GrB activity as a direct way to monitor initiation of effective immune responses. Anti–programmed death-ligand 1 (PD-L1) antibody–conjugated GNRs inhibited PD-1/PD-L1 interactions efficiently and induced T cell–mediated GrB release that can be imaged using activatable imaging probe. GNRs enabled real-time immunotherapy response monitoring in a tumor-bearing mice model and distinguished between highly responsive and poorly responsive tumors. Furthermore, increasing doses resulted in a better response and enhanced sensitivity in poorly responsive tumors. These findings indicate that GNR has the potential to serve as a tool for sensitive and noninvasive evaluation of immunotherapy efficacy.
Science Advances 2020