This paper is only available as a PDF. To read, Please Download here.
Background
Ewing Sarcoma (ES) patients with disseminated disease into lung and bone have an approximate
long-term survival rate of 10–30%, compelling the search for new therapeutic treatment
modalities including engineered T cell therapy. Here, the specific recognition and
lytic potential of transgenic allo-restricted CD8+ T cells directed against the ES-associated
antigen STEAP1 was examined.
Methods
Following repetitive STEAP1130 peptide-driven stimulations with HLA-A∗0201+ dendritic cells, allo-restricted HLA-A∗0201- CD8+ T cells were sorted with HLA-A∗0201/peptide multimers and expanded by limiting dilution. After functional analysis
of suitable T cell clones via ELISpot, flow cytometry and xCelligence assay, TCR α and β chains were identified, cloned into retroviral vectors, codon optimised, transfected
into HLA-A∗0201– primary T cell populations and tested again for specificity and lytic capacity.
Results
Initially generated as well as transgenic T cells specifically recognised STEAP1130
pulsed or transfected cells in the context of HLA-A∗0201 with minimal cross-reactivity as determined by specificinterferon (IFN)-γ release, lysed cells and inhibited growth of HLA-A∗0201+ ES lines more effectively than HLA-A∗0201– ES lines.
Conclusion
Our results identify TCRs capable of recognising and inhibiting growth of STEAP1 expressing
HLA-A∗0201+ ES cells in a highly restricted manner. Such STEAP1 specific TCRs are potentially
useful for immunotherapy of other STEAP1 expressing tumours
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
