Work

Use of a Foamy‐Virus Vector System to Produce an ‘Off‐the‐Shelf’ Fcγ‐ CR ‐T Cell Product for the Treatment of Haematological and Solid Tumour Malignancies

Year: 2025

Type: article

Abstract: The emergence of chimeric antigen receptor (CAR)-T cells has revolutionised the therapeutic landscape of hematologic malignancies, with limited translation only to solid organ malignancies. Furthermore, safety concerns have recently been raised, in terms of tumorigenesis, relating to the viral vector systems used for gene transduction, underlying the need for alternative, safer gene therapy delivery systems. In this study, we investigated the use of foamy virus (FV) vectors, known for their favourable integration profile and reduced genotoxicity, to generate Fcγ (CD16)-chimeric receptor (CR) T cells. Our aim was to provide T cells with the capacity to recognise and bind to tumour cells, opsonised with commercially available monoclonal antibodies (mAbs), enhancing the antibody-dependent cell cytotoxicity (ADCC). The high-affinity F158V polymorphism of the CD16, previously shown to mediate superior ADCC, was utilised for the generation of Fcγ (CD16)-CR T cells. Results showed that FV-derived CD16-CR T cells exhibited robust CD16 expression and demonstrated potent functional activity, including: (i) high mAb-binding capacity, (ii) formation of T-cell tumour cell aggregates in the presence of mAbs, (iii) significant degranulation and proinflammatory cytokine production upon tumour engagement and (iv) potent, dose-dependent cytotoxic activity against target cells in the presence of mAbs. This is the first study, to our knowledge, demonstrating that FV vectors can be used to generate potent CD16-CR T cells, providing a safer and more versatile platform for antibody-based immunotherapy. This approach enables the expansion of engineered T cell therapies beyond hematologic malignancies and towards solid tumours, using clinically approved mAbs.

Source: Immunology

DOI: 10.1111/imm.70018

Authors: Ioanna Lazana, Emmanouil Simantirakis, Evangelos Kourous, Maria Daniil, Dimitris Ioannou, George Vassilopoulos

Institutions: Biomedical Research Foundation of the Academy of Athens, University General Hospital Attikon, University Hospital of Larissa

Language: English

Topic: CAR-T cell therapy research

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $5,330