Format

Send to

Choose Destination
Cancer Res. 2017 May 1;77(9):2318-2327. doi: 10.1158/0008-5472.CAN-16-3346.

Granzyme B PET Imaging as a Predictive Biomarker of Immunotherapy Response.

Author information

1
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts.
2
Department of Medicine, Harvard Medical School, Boston, Massachusetts.
3
Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts.
4
Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts.
5
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts. umahmood@mgh.harvard.edu.

Abstract

While cancer immunotherapy can produce dramatic responses, only a minority of patients respond to treatment. Reliable response biomarkers are needed to identify responders, and conventional imaging modalities have not proved adequate. Here, we provide a preclinical proof of concept for the use of granzyme B, a downstream effector of tumoral cytotoxic T cells, as an early biomarker for tumors responding to immunotherapy. We designed novel PET imaging probes for the murine and human granzyme B isoforms that specifically and quantitatively bind granzyme B. Immunotherapy-treated mice were imaged prior to therapy-induced tumor volume reduction. Imaging distinguished treated responders from nonresponders with excellent predictive ability. To assess the clinical value of a granzyme B imaging paradigm, biopsy specimens from melanoma patients on checkpoint inhibitor therapy were analyzed. A marked differential in granzyme B expression was observed between treated responders and nonresponders. Additionally, our human probe was able to specifically detect granzyme B expression in human samples, providing a clear candidate for clinical application. Overall, our results suggest granzyme B PET imaging can serve as a quantitatively useful predictive biomarker for efficacious responses to cancer immunotherapy. Cancer Res; 77(9); 2318-27. ©2017 AACR.

PMID:
28461564
PMCID:
PMC5474226
DOI:
10.1158/0008-5472.CAN-16-3346
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center