| Title: |
Characterisation of gene-modified CD3-enhanced CD4+ T cells for cancer immunotherapy |
| Authors: |
Piapi, Alice; Nicholson, Emma; Morris, Emma C; Stauss, Hans J |
| Source: |
The Journal of Immunology ; volume 198, issue Supplement_1, page 198.9-198.9 ; ISSN 0022-1767 1550-6606 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2017 |
| Description: |
TCR gene transfer is used to redirect the antigen specificity of T lymphocytes towards known tumour antigens. TCR gene therapies in murine studies have shown promising results. However, in the clinic they often generate sub-optimal responses, when compared to treatments with tumour infiltrating lymphocytes. Previous work to improve TCR gene therapy has demonstrated that transferring additional CD3 genes increases TCR expression of both endogenous and introduced TCR in CD4+ and CD8+ T cells. In vivo experiments demonstrated that CD8+ T cells, transduced with TCR and additional CD3 were more effective in tumour protection than T cells transduced with the TCR alone. Whilst, CD4+ T cells transduced with TCR and additional CD3 initially showed improved tumour protection, lethal toxicity, unrelated to tumour burden, was later observed. To investigate the effects of CD3 overexpression, CD3 genes only (no TCR genes) were transferred into purified CD4+ and CD8+ T cells. Following adoptive transfer, CD3-enhanced CD4+ T cells survived for longer and were recovered in higher percentages in spleen, lymph nodes, bone marrow and liver, compared to CD3-enhanced CD8+ T cells and mock transduced CD4+ T cells. The same trend was also seen in competition experiments where mice received a 1:1 ratio of CD3-enhanced CD4+ T cells and mock-transduced CD4+ T cells. Interestingly, this was observed despite a twofold downregulation of TCR levels in the CD3-enhanced CD4+ T cells, compared to their pre-transfer TCR levels. Current experiments are aimed at dissecting the mechanisms responsible for, and the physiological implications of the observed TCR downregulation. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.4049/jimmunol.198.supp.198.9 |
| Availability: |
https://doi.org/10.4049/jimmunol.198.supp.198.9; https://academic.oup.com/jimmunol/article/198/Supplement_1/198.9/7971472 |
| Rights: |
https://academic.oup.com/pages/standard-publication-reuse-rights |
| Accession Number: |
edsbas.7C211E6 |
| Database: |
BASE |