Detection of immune-mediated tumour cell death in vivo using Zirconium-89-labeled APOMAB®
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, APOMAB®, targets dead tumour cells following DNA-damaging an...
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BMC
2025-06-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06684-z |
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| author | Vasilios Liapis Nicole L. Wittwer William Tieu Tessa Gargett Michael P. Brown Alexander H. Staudacher |
| author_facet | Vasilios Liapis Nicole L. Wittwer William Tieu Tessa Gargett Michael P. Brown Alexander H. Staudacher |
| author_sort | Vasilios Liapis |
| collection | DOAJ |
| description | 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, APOMAB®, 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. Co-culture of GD2-specific chimeric antigen receptor (CAR) T-cells with GD2-expressing cancer cell lines demonstrated specific and dose-dependent binding of APOMAB to the resulting dead target cells, confirming detection of immune-mediated 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 first 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. |
| format | Article |
| id | doaj-art-d24692695e564aad9cad47e6e2a80e2a |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-d24692695e564aad9cad47e6e2a80e2a2025-08-20T03:42:52ZengBMCJournal of Translational Medicine1479-58762025-06-0123111810.1186/s12967-025-06684-zDetection of immune-mediated tumour cell death in vivo using Zirconium-89-labeled APOMAB®Vasilios Liapis0Nicole L. Wittwer1William Tieu2Tessa Gargett3Michael P. Brown4Alexander H. Staudacher5Translational Oncology Laboratory, Centre for Cancer Biology, SA Pathology and University of South AustraliaTranslational Oncology Laboratory, Centre for Cancer Biology, SA Pathology and University of South AustraliaSchool of Physical Sciences, University of AdelaideTranslational Oncology Laboratory, Centre for Cancer Biology, SA Pathology and University of South AustraliaTranslational Oncology Laboratory, Centre for Cancer Biology, SA Pathology and University of South AustraliaTranslational Oncology Laboratory, Centre for Cancer Biology, SA Pathology and University of South AustraliaAbstract 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, APOMAB®, 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. Co-culture of GD2-specific chimeric antigen receptor (CAR) T-cells with GD2-expressing cancer cell lines demonstrated specific and dose-dependent binding of APOMAB to the resulting dead target cells, confirming detection of immune-mediated 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 first 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.https://doi.org/10.1186/s12967-025-06684-z89ZirconiumAPOMABImmunotherapyCAR-T cell therapyPET-imaging |
| spellingShingle | Vasilios Liapis Nicole L. Wittwer William Tieu Tessa Gargett Michael P. Brown Alexander H. Staudacher Detection of immune-mediated tumour cell death in vivo using Zirconium-89-labeled APOMAB® Journal of Translational Medicine 89Zirconium APOMAB Immunotherapy CAR-T cell therapy PET-imaging |
| title | Detection of immune-mediated tumour cell death in vivo using Zirconium-89-labeled APOMAB® |
| title_full | Detection of immune-mediated tumour cell death in vivo using Zirconium-89-labeled APOMAB® |
| title_fullStr | Detection of immune-mediated tumour cell death in vivo using Zirconium-89-labeled APOMAB® |
| title_full_unstemmed | Detection of immune-mediated tumour cell death in vivo using Zirconium-89-labeled APOMAB® |
| title_short | Detection of immune-mediated tumour cell death in vivo using Zirconium-89-labeled APOMAB® |
| title_sort | detection of immune mediated tumour cell death in vivo using zirconium 89 labeled apomab r |
| topic | 89Zirconium APOMAB Immunotherapy CAR-T cell therapy PET-imaging |
| url | https://doi.org/10.1186/s12967-025-06684-z |
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