Granzyme B nanoreporter for early monitoring of tumor response to immunotherapy

Anh Nguyen, Anujan Ramesh, Sahana Kumar, Dipika Nandi, Anthony Brouillard, Alexandria Wells, Leonid Pobezinsky, Barbara Osborne, Ashish A. Kulkarni
2020 Science Advances  
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
more » ... –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.
doi:10.1126/sciadv.abc2777 pmid:33008894 fatcat:owmxx7xotfh47gcdpo65q3joq4