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Updated: Jun 2, 2026
05:20
A Colorimetric Assay that Specifically Measures Granzyme B Proteolytic Activity: Hydrolysis of Boc-Ala-Ala-Asp-S-Bzl
Published on: November 28, 2014
Targeting Cytotoxic T-Cell Effector Function with Granzyme B PET: Translational Advances Toward Predicting
Luca Filippi1,2, Priscilla Guglielmo3,4, Esra Arslan5
1Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier, 1, 00133, Rome, Italy. luca.filippi@uniroma2.it.
Molecular Diagnosis & Therapy
|June 1, 2026
Summary
Granzyme B (GzmB) PET imaging offers a novel way to track anti-tumor immune activity. This approach shows early promise in predicting cancer immunotherapy response before tumor shrinkage is visible.
Area of Science:
- Oncology
- Immunology
- Radiochemistry
Background:
- Cancer immunotherapy success necessitates biomarkers for dynamic immune activity.
- Granzyme B (GzmB) is a key marker of cytotoxic T lymphocyte and NK cell effector function.
- Current imaging methods have limitations in assessing immune response spatially and temporally.
Purpose of the Study:
- To evaluate Granzyme B (GzmB) Positron Emission Tomography (PET) as a non-invasive biomarker for anti-tumor immune activity.
- To assess the potential of GzmB PET for early prediction of response to cancer immunotherapies.
- To explore the feasibility and safety of GzmB PET in clinical settings.
Main Methods:
- Development and preclinical testing of ⁶⁸Ga- and ¹⁸F-labeled peptide-based GzmB PET tracers (e.g., [⁶⁸Ga]Ga-NOTA-GZP, [¹⁸F]AlF-mNOTA-GZP).
- Evaluation of tracer performance in discriminating responders from non-responders to immune checkpoint blockade and combination therapies.
- Initiation of first-in-human studies across various tumor types.
Main Results:
- Preclinical studies consistently showed early discrimination of treatment responders versus non-responders.
- GzmB PET detected immune activity preceding tumor shrinkage or metabolic changes on [¹⁸F]FDG PET.
- Emerging human data support GzmB PET's feasibility, safety, and predictive value in multiple cancers.
Conclusions:
- GzmB PET is a promising tool for non-invasive, whole-body assessment of cytotoxic immune activity in vivo.
- GzmB PET facilitates early response assessment and patient stratification in precision immuno-oncology.
- Further research is needed to address challenges like optimal timing, signal heterogeneity, and standardization for multicenter validation.
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