In vivo bioluminescence imaging of granzyme B activity in tumor response to cancer immunotherapy

Min Chen; Kaixiang Zhou; Sheng-Yao Dai; Sirimuvva Tadepalli; Preethi Bala Balakrishnan; Jinghang Xie; Fadi E I Rami; Tingting Dai; Liyang Cui; Juliana Idoyaga; Jianghong Rao

doi:10.1016/j.chembiol.2022.08.006

In vivo bioluminescence imaging of granzyme B activity in tumor response to cancer immunotherapy

Cell Chem Biol. 2022 Oct 20;29(10):1556-1567.e6. doi: 10.1016/j.chembiol.2022.08.006. Epub 2022 Sep 13.

Authors

Affiliations

¹ Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA 94305, USA.
² Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
³ Department of Chemistry, Stanford University, Stanford, CA 94305, USA.
⁴ Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Chemistry, Stanford University, Stanford, CA 94305, USA. Electronic address: jrao@stanford.edu.

Abstract

Cancer immunotherapy has revolutionized the treatment of cancer, but only a small subset of patients benefits from this new treatment regime. Imaging tools are useful for early detection of tumor response to immunotherapy 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 carcinoma. The GBLI-2 signal correlated with the change in the population of PD-1- and granzyme B-expressing CD8⁺ T cells in tumors.

Keywords: bioluminescence imaging; cancer immunotherapy; checkpoint inhibitor blockade; cytotoxic T lymphocytes; granzyme B.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD8-Positive T-Lymphocytes
Cell Line, Tumor
Granzymes
Immune Checkpoint Inhibitors
Immunotherapy / methods
Mice
Neoplasms*
Programmed Cell Death 1 Receptor*

Substances

Granzymes
Programmed Cell Death 1 Receptor
Immune Checkpoint Inhibitors

Abstract

Publication types

MeSH terms

Substances

Grants and funding