Boosting CAR T cell functionality with oncolytic viruses for the treatment of pediatric diffuse midline gliomas
= 6 cultures), with minimal effect on the viability of B7H3- or GD2-targeted CAR T cells, even at high virus concentrations. In addition, RNA sequencing of infected tumor cells revealed altered gene expression in cell cycle and antiviral response pathways. Furthermore, co-cultures of CAR T cells with OV-infected DMGs enhanced CAR T-specific anti-tumor killing in 14 out of 24 cases. The successful combinations exhibited enhanced cytokine and chemokine release, coupled with an increased cytotoxic phenotype. These findings highlight the benefit of DMG pre-infection with OVs to boost CAR T cell activity and suggest that immune stimulation is a key driver of enhanced combination responses.
Authors
- Rob C. Hoeben (ORCID: https://orcid.org/0000-0001-9443-8377)
- Konstantinos Vazaios (ORCID: https://orcid.org/0000-0002-3623-0348)
- Piotr Waranecki (ORCID: https://orcid.org/0000-0002-0133-9490)
- Annelisa M. Cornel (ORCID: https://orcid.org/0000-0001-8349-121X)
- Esther Hulleman (ORCID: https://orcid.org/0000-0001-9256-947X)
- Jasper van der Lugt (ORCID: https://orcid.org/0000-0002-8186-338X)
- Stefan Nierkens (ORCID: https://orcid.org/0000-0003-3406-817X)
- Marliek van Hoesel
- Noël M.M. Dautzenberg
- Louisa P.J. van Oosterhout
- Antonio C. Tallon Cobos
- Caitlyn Forbes
- Friso G. Calkoen
- Vera Kemp
Institutions
- Leiden University Medical Center (NL)
- University Medical Center Utrecht (NL)
- Princess Máxima Center (NL)
Publication Details
- Journal
- Molecular Therapy Oncology
- Published
- 2026-03-31
- DOI
- https://doi.org/10.1016/j.omton.2026.201191
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Stichting Prinses Máxima Centrum