Publication Date
12-19-2024
Journal
Molecular Therapy Oncology
DOI
10.1016/j.omton.2024.200899
PMID
39624055
PMCID
PMC11609364
PubMedCentral® Posted Date
10-28-2024
PubMedCentral® Full Text Version
Post-Print
Published Open-Access
yes
Keywords
MT: Regular Issue, oncolytic Newcastle disease virus, CAR-T cell, immunotherapy, combination therapy, non-small cell lung carcinoma
Abstract
Systemic administration of oncolytic viruses (OVs) is a promising approach for targeting metastatic solid tumors, but their anti-tumor activity is limited by pre-existing neutralizing antibodies against common human viruses. Therefore, investigators have developed OVs derived from non-human host viruses. Successful implementation of this strategy requires that the viral vector selectively infects and replicates within human cancer cells. Newcastle disease virus (NDV) is an avian paramyxovirus that, as NDV-based OVs (oNDVs), has demonstrated safety and activity against multiple human tumors in clinical trials. Their use as a single agent, however, is insufficient to cure tumors. Similarly, chimeric antigen receptor-modified T cells (CAR-T cells) enable systemic targeting of cancer cells but have limited anti-tumor effects against bulky solid tumors, in part due to the immunosuppressive tumor environment. In this study, we evaluated the anti-tumor effects of combining systemic oNDV and CAR-T cell treatments. In models of non-small cell lung carcinoma (NSCLC), we found that oNDV itself and interleukin (IL)-12 derived from oNDVs enhance HER2-directed CAR-T cell anti-tumor activity and persistence in vitro and in vivo, leading to superior control of NSCLC tumors compared with either agent alone in vivo. Our data indicate that oNDV enhances the anti-tumor effects of HER2.CAR-T cells, thus controlling the growth of orthotopic NSCLC tumors.
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Geriatrics Commons, Immunotherapy Commons, Internal Medicine Commons, Medical Sciences Commons
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