Watson, Heulwen Angharad, Wehenkel, Sophie, Matthews, James and Ager, Elizabeth  ORCID: https://orcid.org/0000-0002-5763-8908
2016.
SHP-1: the next checkpoint target for cancer immunotherapy?
Biochemical Society Transactions
44
(2)
, pp. 356-362.
10.1042/BST20150251
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Abstract
The immense power of the immune system is harnessed in healthy individuals by a range of negative regulatory signals and checkpoints. Manipulating these checkpoints through inhibition has resulted in striking immune-mediated clearance of otherwise untreatable tumours and metastases; unfortunately, not all patients respond to treatment with the currently available inhibitors of cytotoxic T-lymphocyteassociated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). Combinatorial studies using both anti-CTLA-4 and anti-PD-1 demonstrate synergistic effects of targeting multiple checkpoints, paving the way for other immune checkpoints to be targeted. Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1) is a widely expressed inhibitory protein tyrosine phosphatase (PTP). In T-cells, it is a negative regulator of antigen-dependent activation and proliferation. It is a cytosolic protein, and therefore not amenable to antibody-mediated therapies, but its role in activation and proliferation makes it an attractive target for genetic manipulation in adoptive transfer strategies, such as chimeric antigen receptor (CAR) T-cells. This review will discuss the potential value of SHP-1 inhibition in future tumour immunotherapy.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Medicine |
| Subjects: | R Medicine > R Medicine (General) |
| Publisher: | Portland Press |
| ISSN: | 0300-5127 |
| Funders: | Wellcome Trust, Medical Research Council UK |
| Date of First Compliant Deposit: | 23 May 2016 |
| Date of Acceptance: | 5 February 2016 |
| Last Modified: | 05 May 2023 01:28 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/90623 |
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