Detection of immune-mediated tumour cell death in vivo using Zirconium-89-labeled APOMABĀ®
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Date
2025
Authors
Liapis, V.
Wittwer, N.L.
Tieu, W.
Gargett, T.
Brown, M.P.
Staudacher, A.H.
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Journal article
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Journal of Translational Medicine, 2025; 23(1, article no. 651):651-1-651-18
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Vasilios Liapis, Nicole L. Wittwer, William Tieu, Tessa Gargett, Michael P. Brown, and Alexander H. Staudacher
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Abstract
Background Inconsistent responses to anticancer immunotherapies demonstrate the need for non-invasive methods to detect treatment responses earlier than conventional medical imaging methods allow. The chimeric monoclonal antibody, APOMABĀ®, targets dead tumour cells following DNA-damaging anticancer treatments via binding of the ribonuclear protein, La/SSB, an intracellular protein overexpressed by tumour cells. La/SSB only becomes accessible to APOMAB binding in post-apoptotic necrotic tumour cells. Methods We assessed the ability of APOMAB to detect dead tumour cells after immune-mediated cell death. Coculture of GD2-specifc chimeric antigen receptor (CAR) T-cells with GD2-expressing cancer cell lines demonstrated specifc and dose-dependent binding of APOMAB to the resulting dead target cells, confrming detection of immunemediated cell death. Then, using four distinct preclinical tumour models and in a cancer patient, we investigated APOMAB-immunoPET as a technique to detect immune-mediated tumour cell death. Results Within days of treatment, APOMAB-immunoPET showed increased tumour uptake of 89Zirconium-labelled APOMAB (89Zr-APOMAB) after CAR-T cell therapy, immune checkpoint inhibitor (ICI) therapy with and without chemotherapy, and via endogenous T-cell mediated tumour clearance. In a metastatic melanoma patient after ICI therapy, a previously FDG-avid pulmonary tumour reduced in size as tumour 89Zr-APOMAB uptake increased over the 12-day scanning period. Conclusions This study demonstrates for the frst time that not only does radiolabelled APOMAB provide an initial direct measure of the extent of immune-mediated tumour cell death in vivo but also reveals the heterogeneous nature of tumour responses to T-cell based therapies both within and between individuals.
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Data source: Supplementary Information, https://doi.org/10.1186/s12967-025-06684-z
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Ā© Crown 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the articleās Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the articleās Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.