Bayliss, Rebecca J.  ORCID: https://orcid.org/0000-0002-3324-957X, Badder, Luned M., Davies, James ORCID: https://orcid.org/0000-0003-3569-4500, Robinson, Andrew, Pissarreck, Mona, Kollnberger, Simon and Parker, Alan L. ORCID: https://orcid.org/0000-0002-9302-1761
2025.
An αvβ6 specific precision virotherapy expressing bispecific immune cell activators induces immune cell activation and mediates tumour cell death.
Molecular Therapy Oncology
, 201017.
10.1016/j.omton.2025.201017
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Abstract
Ad5NULL-A20 is an Adenovirus type 5 based precision virotherapy engineered to selectively target αvβ6 positive tumours. Bispecific immune cell activators (BICA) bind both an immune cell receptor and tumour cell-associated antigen (TAA) in tandem to induce a tumour-specific immune response. Combining the selectivity and oncolytic properties of Ad5NULL-A20 with the potency of BICA will create a more tolerated, enduring immune cell response limited to tumour sites, reducing off target effects and dose limiting toxicities. We developed multiple BICA targeting T-cells via CD3, Natural killer (NK cells) via CD16/NKG2D receptors and TAA Epidermal growth factor receptor (EGFR) and Major histocompatibility complex related chain A (MICA). In vitro studies establish that Ad5NULL-A20 BICA in αvβ6 tumour cells, results in T-cell and NK activation at tumour sites and a loss of tumour cell viability. Ex vivo studies validate these findings demonstrating a significant and rapid reduction in growth of patient-derived 3D tumour organoids transduced with oncolytic Ad5NULL-A20-BICA in the presence of T- or NK- cells. Ad5NULL-A20 expressing BICA can produce a potent immune response resulting in tumour eradication. This approach has significant translational potential to develop a novel cancer therapeutic for clinical success.
| Item Type: | Article |
|---|---|
| Date Type: | Published Online |
| Status: | In Press |
| Schools: | Schools > Medicine |
| ISSN: | 2950-3299 |
| Funders: | Cancer Research UK |
| Date of First Compliant Deposit: | 27 June 2025 |
| Date of Acceptance: | 23 June 2025 |
| Last Modified: | 03 Jul 2025 12:15 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/179349 |
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