Journal
CELL CHEMICAL BIOLOGY
Volume 29, Issue 10, Pages 1556-+Publisher
CELL PRESS
DOI: 10.1016/j.chembiol.2022.08.006
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Funding
- NIH [U54CA199075, R01CA243033, R01CA219994]
- Stanford Cancer Translational Nanotechnology Training Program - NCI award [T32CA196585]
- CDMRP Breast Cancer Research Program Break through postdoctoral fellowship award [W81XWH1810591]
- Life Sciences Research Foundation
- Center for Molecular Analysis and Design (CMAD) at Stanford
- U.S. Department of Defense (DOD) [W81XWH1810591] Funding Source: U.S. Department of Defense (DOD)
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This study presents a bioluminescence probe, GBLI-2, for real-time imaging of granzyme B activity in tumors undergoing immune checkpoint inhibitor therapy. The GBLI-2 signal correlated with changes in the population of PD-1 and granzyme B-expressing CD8+ T cells in tumors.
Cancer immunotherapy has revolutionized the treatment of cancer, but only a small subset of patients ben-efits from this new treatment regime. Imaging tools are useful for early detection of tumor response to immu-notherapy and probing the dynamic and complex immune system. Here, we report a bioluminescence probe (GBLI-2) for non-invasive, real-time, longitudinal imaging of granzyme B activity in tumors receiving immune checkpoint inhibitors. GBLI-2 is made of the mouse granzyme B tetrapeptide IEFD substrate conjugated to D-luciferin through a self-immolative group. GBLI-2 was evaluated for imaging the dynamics of the granzyme B activity and predicting therapeutic efficacy in a syngeneic mouse model of CT26 murine colorectal carci-noma. The GBLI-2 signal correlated with the change in the population of PD -1-and granzyme B-expressing CD8+ T cells in tumors.
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