This paper is only available as a PDF. To read, Please Download here.
Hepatocellular carcinoma is highly resistant to conventional therapies and need alternative
treatments. Oncolytic viruses are promising tools for the treatment for solid tumours
but unfortunately trigger strong T cell immune responses against the applied virus.
Here, we wanted to investigate whether antiviral cytotoxic T lymphocytes triggered
by oncolytic virotherapy can be redirected with a tumour specific TCR for therapy
of HCC in an immunocompetent C57BL/6 mouse model.
First, virus-specific T cells were induced by intraperitoneal challenge with oncolytic
Adenovirus in Thy1.1. mice and splenocytes were used to generate bispecific T cells
by lentiviral transfer of the OT-1 receptor in adenovirus-specific T cells. Resulting
bispecific T cells were adoptively transferred into Thy1.2 recipient mice bearing
HCC tumours expressing OVA minimum epitopes. Prior to Adoptive transfer, mice were
preconditioned with Cyclophosphamid and Treosulfan to achieve lymphoreduction.
Tracking lentiviral encoded GFP and CD8 by FACS analysis, we showed establishment
of transduced CD8 T cells in blood, spleen and tumour tissue. Finally we demonstrated
that, compared with naïve and immunized mock-transduced cohorts, the group which received
Ad/OT-1 specific T cells showed significantly improved regression and long-term survival.
Our findings suggest that virus-specific T cells induced by oncolytic virotherapy
can be successfully redirected with a tumour specific TCR to address therapy-resistant
HCC.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to European Journal of CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
