5T4 oncofoetal antigen: an attractive target for immune intervention in cancer.
AffiliationInstitute of Cancer Studies, Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester, M20 4BX
MetadataShow full item record
AbstractThe natural history of a patient's cancer is often characterised by genetic diversity and sequential sweeps of clonal dominance. It is therefore not surprising that identifying the most appropriate tumour-associated antigen for targeted intervention is challenging. The 5T4 oncofoetal antigen was identified by searching for surface molecules shared between human trophoblast and cancer cells with the rationale that they may function to allow survival of the foetus as a semi-allograft in the mother or a tumour in its host. The 5T4 protein is expressed by many different cancers but rarely in normal adult tissues. 5T4 molecules are 72 kD, heavily N-glycosylated proteins with several leucine-rich repeats which are often associated with protein-protein interactions. 5T4 expression is associated with the directional movement of cells through epithelial mesenchymal transition, potentiation of CXCL12/CXCR4 chemotaxis and inhibition of canonical Wnt/beta-catenin while favouring non-canonical pathway signalling; all processes which help drive the spread of cancer cells. The selective pattern of 5T4 tumour expression, association with a tumour-initiating phenotype plus a mechanistic involvement with cancer spread have underwritten the clinical development of different immunotherapeutic strategies including a vaccine, a tumour-targeted superantigen and an antibody drug conjugate. In addition, a chimeric antigen receptor T cell approach targeting 5T4 expressing tumour cells is in pre-clinical development. A key challenge will include how best to combine each 5T4 targeted immunotherapy with the most appropriate standard of care treatment (or adjunct therapy) to maximise the recovery of immune control and ultimately eliminate the tumour.
Citation5T4 oncofoetal antigen: an attractive target for immune intervention in cancer. 2016: Cancer Immunol. Immunother.
JournalCancer Immunology, Immunotherapy
- Understanding and exploiting 5T4 oncofoetal glycoprotein expression.
- Authors: Stern PL, Brazzatti J, Sawan S, McGinn OJ
- Issue date: 2014 Dec
- Characterization of the murine 5T4 oncofoetal antigen: a target for immunotherapy in cancer.
- Authors: Woods AM, Wang WW, Shaw DM, Ward CM, Carroll MW, Rees BR, Stern PL
- Issue date: 2002 Aug 15
- 5T4 oncofoetal glycoprotein: an old target for a novel prostate cancer immunotherapy.
- Authors: Cappuccini F, Pollock E, Stribbling S, Hill AVS, Redchenko I
- Issue date: 2017 Jul 18
- Expression of the 5T4 oncofoetal antigen in renal cell carcinoma: a potential target for T-cell-based immunotherapy.
- Authors: Griffiths RW, Gilham DE, Dangoor A, Ramani V, Clarke NW, Stern PL, Hawkins RE
- Issue date: 2005 Sep 19
- CXCL12 receptor preference, signal transduction, biological response and the expression of 5T4 oncofoetal glycoprotein.
- Authors: McGinn OJ, Marinov G, Sawan S, Stern PL
- Issue date: 2012 Nov 15