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Cancer Immunology, Immunotherapy

, Volume 66, Issue 4, pp 415–426 | Cite as

5T4 oncofoetal antigen: an attractive target for immune intervention in cancer

  • Peter L. Stern
  • Richard HarropEmail author
Review

Abstract

The 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.

Keywords

5T4 oncofetal antigen Trophoblast glycoprotein (TBPG) Cancer vaccine Chimeric antigen receptors Antibody drug targeting Superantigen therapy 

Abbreviations

ADC

Antibody drug conjugate

ALL

Acute lymphoblastic leukaemia

BCP

B-cell precursor

CAR

Chimeric antigen receptor

CRP

C-reactive protein

EMT

Epithelial mesenchyme transition

ES

Embryonic stem

IHC

Immunohistochemistry

kD

Kilodalton

KO

Knock-out

LRR

Leucine-rich repeat

MSKCC

Memorial Sloan Kettering Cancer Center

MTD

Maximum tolerated dose

MVA

Modified vaccinia Ankara

NCI

National Cancer Institute

NSCLC

Non-small cell lung cancer

RCC

Renal cell carcinoma

SEA

Staphylococcal enterotoxin A

TBPG

Trophoblast glycoprotein

TIC

Tumour-initiating cell

Treg

Regulatory T cell

VEGF

Vascular endothelial growth factor

Notes

Compliance with ethical standards

Conflict of interest

Author Richard Harrop is employed by Oxford BioMedica who is developing 5T4-targeted therapies. Peter L. Stern is a consultant for Oxford BioMedica and has received speaker honoraria from Pfizer.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Institute of Cancer Studies, Paterson Institute for Cancer ResearchUniversity of ManchesterManchesterUK
  2. 2.Oxford BioMedica PlcOxfordUK

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