Affinage

TPBG

Trophoblast glycoprotein · UniProt Q13641

Length
420 aa
Mass
46.0 kDa
Annotated
2026-06-10
100 papers in source corpus 18 papers cited in narrative 17 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TPBG (5T4/WAIF1) is a heavily N-glycosylated type I transmembrane glycoprotein whose leucine-rich-repeat extracellular domain and short cytoplasmic tail integrate cell-surface signaling with cytoskeletal and membrane-trafficking control, acting as a regulator of cell motility, epithelial-mesenchymal transition (EMT), and developmental signaling (PMID:8132670, PMID:17507657, PMID:22100263). The mature protein is a ~72 kDa glycoprotein built on a ~42–46 kDa core whose extensive, largely complex N-glycosylation confers protease resistance, and its extracellular region folds into a rigid eight-LRR core resolved by crystallography at 1.8 Å (PMID:2298503, PMID:8132670, PMID:11903056, PMID:24582434). Surface delivery of 5T4 is gated by E-cadherin-mediated cell-cell adhesion: loss of E-cadherin contacts during EMT drives energy-dependent translocation of 5T4 to the cell surface, where it disrupts actin/cadherin junctions and increases motility, with the cytoplasmic tail required for junction disruption but dispensable for the motility effect (PMID:8895545, PMID:17507657). The cytoplasmic tail carries a class I PDZ-binding motif (terminal valine) that recruits the PDZ protein TIP-2/GIPC, linking 5T4 to the actin cytoskeleton, while interactions with Rab11, Rab18 and ARF6 control 5T4's own endocytic trafficking and surface levels (PMID:11798178, PMID:29549047). At the cell surface 5T4 organizes chemokine signaling by promoting functional CXCR4 surface expression and CXCL12-driven chemotaxis—an activity for which the transmembrane domain is necessary and sufficient—thereby steering CXCL12 responses away from a CXCR7/EGFR-transactivation/proliferation axis toward a CXCR4/ERK/AKT/chemotaxis axis (PMID:20376365, PMID:22956548). As WAIF1, 5T4 binds the Wnt co-receptor LRP6 and blocks its Wnt-induced internalization, suppressing canonical Wnt/β-catenin signaling while promoting non-canonical Wnt output, with LRR1 surface residues Tyr325 and Phe97 essential for this inhibition (PMID:22100263, PMID:24582434). These activities underlie roles in EMT and metastasis, embryonic differentiation, hypoxia-driven pericyte angiogenic behavior, and activity-dependent dendritic development of olfactory bulb interneurons (PMID:17507657, PMID:22323733, PMID:31018661).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1990 High

    Establishing that the 5T4 antigen is a single heavily N-glycosylated glycoprotein defined the molecule biochemically and explained its unusual protease resistance.

    Evidence Lectin/immunoaffinity purification, deglycosylation, and protease assays on the native antigen

    PMID:2298503

    Open questions at the time
    • Primary sequence and domain organization not yet known
    • No functional role assigned
  2. 1994 High

    cDNA cloning revealed 5T4 as a type I transmembrane LRR protein, providing the structural framework for all later mechanistic work.

    Evidence cDNA cloning from a human placental library guided by purified-protein sequence, with sequence analysis

    PMID:8132670

    Open questions at the time
    • No interaction partners identified
    • Function of LRR domain and cytoplasmic tail unknown
  3. 1995 Medium

    Forced expression linked 5T4 to a motility/adhesion phenotype, indicating it is not merely a tumor marker but an active modulator of cell behavior.

    Evidence Stable 5T4 transfection into L cells with confocal and electron microscopy of microvillus localization and motility/adhesion assays

    PMID:7593330

    Open questions at the time
    • Mechanism connecting surface localization to motility unresolved
    • Single-lab gain-of-function only
  4. 1996 High

    Domain-deletion separated 5T4's two outputs—the cytoplasmic tail abrogates actin/cadherin contacts while motility effects map elsewhere—showing the protein signals through distinct domains.

    Evidence Full-length vs cytoplasmic-deleted 5T4 transfected into mammary and MDCK epithelial cells with morphology and motility readouts

    PMID:8895545

    Open questions at the time
    • Cytoplasmic-tail effector not identified
    • Extracellular determinant of motility undefined
  5. 2002 High

    Identification of the TIP-2/GIPC PDZ interaction gave the first molecular link between 5T4's tail and the actin cytoskeleton.

    Evidence Yeast two-hybrid, PDZ-motif mutagenesis, co-IP, and co-localization in HeLa cells

    PMID:11798178

    Open questions at the time
    • Functional consequence of GIPC binding for motility/junctions not directly tested
    • Link to downstream actin regulators unmapped
  6. 2002 High

    Defining glycan occupancy and mapping the antibody epitope characterized the surface architecture of the extracellular domain.

    Evidence Glycan compositional analysis plus deletion/chimera epitope mapping

    PMID:11903056

    Open questions at the time
    • Functional role of specific glycans not tested
    • No 3D structure yet
  7. 2003 Medium

    Developmental upregulation upon ES cell differentiation tied 5T4 expression to early morphogenetic transitions and confirmed actin-dependence of its phenotype.

    Evidence FACS/RT-PCR on differentiating ES cells plus transfection into melanoma/fibroblast lines with cytochalasin D actin disruption

    PMID:12003637 PMID:14576347

    Open questions at the time
    • Signaling pathway driving morphology change undefined
    • Single-lab gain-of-function
  8. 2007 High

    E-cadherin contacts were shown to gate 5T4 surface localization, embedding 5T4 in the EMT program as an adhesion-controlled surface switch.

    Evidence ES cell EMT models with E-cadherin neutralization, E-cadherin and 5T4 knockouts, and rescue with motility readouts

    PMID:17507657

    Open questions at the time
    • Mechanism of energy-dependent translocation unresolved
    • Trafficking machinery not yet identified
  9. 2010 High

    5T4 was found necessary for functional CXCR4 surface expression and CXCL12 chemotaxis, identifying a transmembrane-domain-mediated chemokine-organizing function.

    Evidence 5T4 knockout ES cells/MEFs with adenoviral rescue and 5T4/CD44 domain-swap chimeras in chemotaxis and co-localization assays

    PMID:20376365

    Open questions at the time
    • Molecular nature of TM-domain/CXCR4 interaction undefined
    • Whether 5T4 directly binds CXCR4 unproven
  10. 2011 High

    As WAIF1, 5T4 was shown to bind LRP6 and block its Wnt-induced internalization, placing 5T4 as a switch between canonical and non-canonical Wnt signaling.

    Evidence Zebrafish/Xenopus gain-loss-of-function, mammalian Wnt reporters, Waif1a–LRP6 co-IP, and LRP6 internalization assays

    PMID:22100263

    Open questions at the time
    • Structural basis of LRP6 binding not yet defined
    • Mechanism of non-canonical DKK1 enhancement unresolved
  11. 2012 High

    5T4 was shown to determine CXCL12 receptor preference (CXCR4 vs CXCR7), dictating chemotaxis versus proliferation outcomes.

    Evidence Wild-type vs 5T4 knockout MEFs with CXCR4/CXCR7 antagonists, ERK/AKT readouts, and human SCLC lines

    PMID:22956548

    Open questions at the time
    • How 5T4 represses CXCR7 expression is unknown
    • Direct receptor contacts not mapped
  12. 2012 High

    5T4 was assigned a neuronal role in activity-dependent dendritic development, with the cytoplasmic domain necessary and sufficient for sensory-input-dependent shaping.

    Evidence Overexpression, RNAi, knockout, and cytoplasmic-domain truncations in olfactory bulb interneurons with dendritic morphometry

    PMID:22323733

    Open questions at the time
    • Cytoplasmic-tail effectors mediating dendritic shaping unidentified
    • Link to activity-dependent signaling pathways unmapped
  13. 2014 High

    The 1.8 Å crystal structure of the LRR ectodomain defined a rigid eight-LRR core and pinpointed LRR1 residues Tyr325/Phe97 as required for Wnt inhibition.

    Evidence X-ray crystallography with structure-guided mutagenesis in Wnt reporter assays

    PMID:24582434

    Open questions at the time
    • Structure of LRP6-bound complex not solved
    • Structural basis of CXCR4/CXCR7 organization not addressed
  14. 2018 Medium

    5T4 was linked to Rab11/Rab18/ARF6 trafficking machinery that controls its own surface levels, revealing a self-regulatory endocytic loop.

    Evidence Co-IP/mass spectrometry, siRNA depletion, transferrin surface labeling, and focal-adhesion localization in breast cancer cells

    PMID:29549047

    Open questions at the time
    • Direct vs indirect nature of Rab interactions unclear
    • Single-lab Co-IP/MS without reciprocal validation
  15. 2015 Medium

    5T4 antigen cross-presentation was shown to be predominantly Hsp70/CD91-dependent, relevant to anti-5T4 immune responses.

    Evidence DC–tumor co-culture cross-presentation with Hsp70 inhibitors, CD91 blockade, and CD8+ T-cell readouts

    PMID:25678582

    Open questions at the time
    • Concerns 5T4 as an antigen, not its intrinsic molecular function
    • Single in vitro model
  16. 2019 High

    In pericytes, hypoxia/CITED2-driven TPBG was shown to act through CXCL12/CXCR7/ERK and induce CXCR7/CXCR4 heterodimers, extending its chemokine-organizing role to angiogenesis in vivo.

    Evidence siRNA/overexpression in primary pericytes, proximity ligation for heterodimers, and Matrigel/limb-ischemia in vivo models

    PMID:31018661

    Open questions at the time
    • Reconciliation with the CXCR4-favoring model from MEFs unresolved
    • Direct 5T4–receptor contacts not mapped
  17. 2018 Medium

    A negative replication challenged the generality of 5T4's CXCL12-organizing role, indicating context-dependence across cancer cell types.

    Evidence siRNA depletion of 5T4 with CXCR4/CXCR7 antagonists across five cancer cell lines failing to alter receptor usage

    PMID:29408206

    Open questions at the time
    • Does not exclude the role in non-transformed/ES cell contexts
    • Mechanistic basis of cell-type dependence unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how 5T4 physically couples a single LRR ectodomain and short tail to its diverse outputs—CXCR4/CXCR7 organization, LRP6 internalization control, and cytoplasmic-tail-dependent dendritic and junctional effects—within a unified mechanism.
  • No structure of 5T4 bound to CXCR4, CXCR7, or LRP6
  • Cytoplasmic-tail effectors beyond GIPC for neuronal/junctional roles unidentified
  • Cell-type determinants of CXCR4 vs CXCR7 preference unexplained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0098772 molecular function regulator activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-5653656 Vesicle-mediated transport 1
Partners
ARF6CXCR4CXCR7GIPC1LRP6RAB11A

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 TPBG/5T4 antigen is a 72 kDa glycoprotein with a 42 kDa core protein; extensive N-linked glycosylation accounts for the molecular weight difference; the native molecule is resistant to proteolysis until N-linked sugars are removed or the glycoprotein is denatured and reduced. Lectin- and immunoaffinity chromatography, gel filtration, SDS-PAGE, N-glycanase treatment, protease digestion assays International journal of cancer High 2298503
1994 TPBG/5T4 cDNA encodes a 420 amino acid type I transmembrane protein (46 kDa predicted, 72 kDa glycosylated) with N- and C-terminal hydrophobic signal/transmembrane segments, 8 potential N-glycosylation sites, and leucine-rich repeats (LRRs) in the extracellular domain. cDNA cloning from human placental library using oligonucleotides based on purified protein sequence; Northern blot analysis; sequence database comparison The Journal of biological chemistry High 8132670
1995 TPBG/5T4 is concentrated at microvillus projections of the plasma membrane in transfected murine L cells (A9 derivative) and in carcinoma cell lines; 5T4 expression in A9 cells is associated with altered cell division, decreased cell-substratum adhesion, and increased cellular motility. Stable transfection of 5T4 cDNA into L cells; confocal immunofluorescence microscopy; transmission and scanning electron microscopy Journal of cell science Medium 7593330
1996 Transfection of full-length 5T4 cDNA into epithelial cells disrupts actin/cadherin-containing cell-cell contacts and increases motility; deletion of the cytoplasmic domain shows that the cytoplasmic tail is necessary for abrogating actin/cadherin contacts but is not required for the effects on motility, indicating that 5T4 can deliver signals through both extracellular and intracellular domains. Stable transfection of full-length and cytoplasmic-domain-deleted 5T4 cDNA into CL-S1 murine mammary cells and MDCK epithelial cells; motility assays; morphological analysis International journal of cancer High 8895545
2002 TPBG/5T4 interacts with TIP-2/GIPC, a cytoplasmic PDZ-domain protein; the interaction requires the C-terminal class I PDZ-binding motif (Ser-Asp-Val) of 5T4, specifically the terminal valine; 5T4 and TIP-2/GIPC co-localize in HeLa cells and can be co-immunoprecipitated, providing the first link between 5T4 and the actin cytoskeleton. Yeast two-hybrid screen; site-directed mutagenesis of PDZ-binding motif; co-immunoprecipitation from HeLa cell lysates; co-localization by immunofluorescence Biochemical and biophysical research communications High 11798178
2002 Glycosylation analysis of 5T4 demonstrates all seven consensus N-glycosylation sites are occupied: two predominantly high-mannose chains and five mostly sialylated bi-, tri- and tetra-antennary complex chains with minor core fucose. The mAb5T4 epitope was mapped to the membrane-proximal LRR2 region or its flanking region using deletion/mutation constructs and human-mouse chimeras. Site-directed mutagenesis; deletion constructs; human-mouse chimeric cDNA constructs; glycan analysis by mass spectrometry/carbohydrate chemistry The Biochemical journal High 11903056
2007 E-cadherin-mediated cell-cell contact prevents cell surface localization of 5T4 antigen; disruption of E-cadherin contacts (by neutralizing antibody or in E-cadherin knockout ES cells) causes translocation of 5T4 from the cytoplasm to the cell surface in an energy-dependent manner; this cell surface localization of 5T4 is associated with increased cellular motility during epithelial-mesenchymal transition. 5T4 knockout ES cells show significantly decreased motility during EMT. Mouse ES cell differentiation; E-cadherin neutralizing antibody; E-cadherin knockout ES cells; forced E-cadherin re-expression; 5T4 knockout ES cells; FACS; motility assays; confocal imaging Molecular biology of the cell High 17507657
2010 TPBG/5T4 is required for optimal functional cell surface expression of CXCR4 and CXCL12-mediated chemotaxis in differentiating mouse embryonic stem cells and embryonic fibroblasts; 5T4 and CXCR4 co-localize at the cell surface; in 5T4 knockout cells CXCR4 is retained intracellularly and CXCL12 chemotaxis is abolished; adenoviral restoration of 5T4 rescues CXCR4 surface expression and chemotaxis; the 5T4 transmembrane domain is sufficient and necessary for CXCR4 membrane expression. 5T4 knockout mouse-derived ES cells and MEFs; adenoviral 5T4 rescue; chimeric 5T4/CD44 domain-swap constructs; CXCL12 chemotaxis assays; co-localization immunofluorescence; FACS PloS one High 20376365
2011 TPBG/5T4 (Waif1) inhibits Wnt/β-catenin signaling and activates non-canonical Wnt pathways; Waif1a binds the Wnt co-receptor LRP6 and inhibits Wnt-induced LRP6 internalization into endocytic vesicles, a process required for canonical Wnt pathway activation; Waif1a also enhances β-catenin-independent Wnt signaling by promoting a non-canonical function of Dickkopf1. Zebrafish and Xenopus embryo gain/loss-of-function; mammalian cell Wnt reporter assays; co-immunoprecipitation of Waif1a with LRP6; LRP6 internalization assays Developmental cell High 22100263
2012 5T4 glycoprotein regulates activity-dependent dendritic development of specific interneuron subtypes in the mouse olfactory bulb; overexpression of 5T4 facilitates dendritic arborization under sensory-deprived conditions; 5T4 knockdown (RNAi) and 5T4 knockout reduce dendritic arborization of 5T4+ granule cells; the cytoplasmic domain of 5T4 contains the sequence necessary and sufficient for sensory input-dependent dendritic shaping. 5T4 overexpression and RNAi knockdown in newborn OB interneurons; 5T4 knockout mice; cytoplasmic domain deletion/truncation constructs; dendritic morphometry The Journal of neuroscience High 22323733
2012 In the absence of 5T4 expression, CXCL12 signaling through CXCR4 (activating ERK and AKT) is non-functional despite intact pathways; CXCR7 is upregulated and becomes the predominant CXCL12 receptor, activating a distinct pathway involving EGFR transactivation and eliciting proliferation rather than chemotaxis; 5T4 surface expression thus determines receptor preference (CXCR4 vs CXCR7) and hence the biological response to CXCL12. Wild-type and 5T4 knockout MEFs; CXCR4 antagonist AMD3100; CXCR7 antagonist CCX771; ERK/AKT pathway phosphorylation assays; chemotaxis and proliferation assays; human SCLC cell lines with 5T4/CXCR7 reciprocity Journal of cell science High 22956548
2014 Crystal structure of the extracellular domain of 5T4/WAIF1 at 1.8 Å resolution reveals a highly glycosylated rigid core comprising eight leucine-rich repeats (LRRs); conserved surface residues in LRR1, particularly Tyr325 and Phe97, are essential for inhibition of Wnt/β-catenin signaling as determined by structural and cell-based analyses. X-ray crystallography at 1.8 Å; cell-based Wnt/β-catenin reporter assays; structure-guided mutagenesis of surface residues Structure High 24582434
2018 5T4 interacts with membrane trafficking proteins Rab11, Rab18, and ARF6 as identified by co-immunoprecipitation and mass spectrometry; Rab11 and Rab18 have opposing roles in controlling 5T4 surface expression; endocytosis of 5T4 is strongly Rab11-dependent; 5T4 depletion stabilizes Rab11 protein expression and stimulates transferrin surface labeling, indicating that 5T4 represses Rab11-mediated endocytic activity. 5T4 localizes to focal adhesions in differentiated breast cancer cells. Co-immunoprecipitation followed by mass spectrometry; flow cytometry; immunofluorescence co-localization; 5T4 siRNA depletion; transferrin surface labeling assay The international journal of biochemistry & cell biology Medium 29549047
2019 TPBG/5T4 expression in adventitial pericyte-like cells is upregulated by hypoxia through the transcriptional modulator CITED2, leading to CXCL12 signaling via CXCR7 and ERK1/2 activation; TPBG silencing downregulates CXCL12, CXCR7, and pERK1/2 and reduces pericyte migratory and proangiogenic capacity; TPBG forced expression induces formation of CXCR7/CXCR4 heterodimers; in vivo, TPBG is essential for angiogenesis (Matrigel plug assay) and perfusion recovery in limb ischemia. siRNA silencing; forced overexpression; proximity ligation assay for CXCR7/CXCR4 heterodimers; ELISA, Western blot, immunocytochemistry; in vivo Matrigel plug assay; murine limb ischemia model Arteriosclerosis, thrombosis, and vascular biology High 31018661
2018 siRNA-mediated depletion of 5T4 in most tested cancer cell lines (A549, C33A, DLD-1, MDA-231, PC-3) did not change the CXCL12 receptor usage or subcellular localization of CXCR4/CXCR7 in the majority of lines, failing to replicate the previously reported general organizational role of 5T4 in the CXCL12 system in cancer cells; however, 5T4 inhibition did modulate migration and proliferation per se in some cell lines. siRNA depletion of 5T4; CXCR4 antagonist AMD3100; CXCR7 antagonist CCX771; chemotaxis and proliferation assays in multiple cancer cell lines Experimental cell research Medium 29408206
2015 Irradiation of 5T4-expressing DU145 prostate cancer cells induces Hsp70 surface expression; cross-presentation of 5T4 antigen by dendritic cells to CD8+ T cells is predominantly Hsp70-dependent: Hsp70 inhibitor pretreatment robustly prevented antigen cross-presentation and CD86 upregulation on DCs; blocking the Hsp70 receptor CD91 also abolished cross-presentation. DC-tumor cell co-culture cross-presentation model; Hsp70 inhibitors; CD91 blocking antibody; CD8+ T cell proliferation and IFN-γ production assays; HMGB1 inhibition; TLR4 SNP analysis Cancer immunology research Medium 25678582
2003 Murine 5T4 antigen expression is absent on undifferentiated ES cells but is rapidly upregulated upon differentiation into all three primary germ layer derivatives; 5T4 expression correlates with early differentiation events involving altered motility and morphology; overexpression of mouse 5T4 in B16 F10 melanoma cells and A9 L fibroblasts produces spindle-like morphology, increased motility, and reduced adhesion and proliferation, dependent on integrity of the actin cytoskeleton. Cell surface FACS, Western blot, RT-PCR on differentiating ES cells; stable transfection of m5T4 in B16 F10 and A9 cells; motility, adhesion, proliferation assays; cytochalasin D actin disruption Journal of cell science / The Biochemical journal Medium 12003637 14576347

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1990 Immunohistological distribution of 5T4 antigen in normal and malignant tissues. British journal of cancer 168 2404511
2010 Vaccination of metastatic renal cancer patients with MVA-5T4: a randomized, double-blind, placebo-controlled phase III study. Clinical cancer research : an official journal of the American Association for Cancer Research 144 20881001
2007 E-cadherin inhibits cell surface localization of the pro-migratory 5T4 oncofetal antigen in mouse embryonic stem cells. Molecular biology of the cell 91 17507657
2011 Waif1/5T4 inhibits Wnt/β-catenin signaling and activates noncanonical Wnt pathways by modifying LRP6 subcellular localization. Developmental cell 80 22100263
1995 5T4 oncofetal antigen expression in ovarian carcinoma. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 77 11578488
2007 Vaccination of colorectal cancer patients with modified vaccinia ankara encoding the tumor antigen 5T4 (TroVax) given alongside chemotherapy induces potent immune responses. Clinical cancer research : an official journal of the American Association for Cancer Research 75 17671134
1992 The expression of 5T4 antigen in colorectal and gastric carcinoma. British journal of cancer 69 1419629
1996 Metastasis-associated 5T4 antigen disrupts cell-cell contacts and induces cellular motility in epithelial cells. International journal of cancer 67 8895545
2006 A leucine-rich repeat membrane protein, 5T4, is expressed by a subtype of granule cells with dendritic arbors in specific strata of the mouse olfactory bulb. The Journal of comparative neurology 66 16506198
1994 Isolation of a cDNA encoding 5T4 oncofetal trophoblast glycoprotein. An antigen associated with metastasis contains leucine-rich repeats. The Journal of biological chemistry 64 8132670
1990 Isolation and characterization of 5T4, a tumour-associated antigen. International journal of cancer 63 2298503
2016 5T4 oncofoetal antigen: an attractive target for immune intervention in cancer. Cancer immunology, immunotherapy : CII 62 27757559
2009 Vaccination of renal cell cancer patients with modified vaccinia Ankara delivering the tumor antigen 5T4 (TroVax) alone or administered in combination with interferon-alpha (IFN-alpha): a phase 2 trial. Journal of immunotherapy (Hagerstown, Md. : 1997) 62 19561532
2005 Expression of the 5T4 oncofoetal antigen in renal cell carcinoma: a potential target for T-cell-based immunotherapy. British journal of cancer 62 16222313
2009 Phase II trial of Modified Vaccinia Ankara (MVA) virus expressing 5T4 and high dose Interleukin-2 (IL-2) in patients with metastatic renal cell carcinoma. Journal of translational medicine 60 19128501
2012 Long-term tumor regression induced by an antibody-drug conjugate that targets 5T4, an oncofetal antigen expressed on tumor-initiating cells. Molecular cancer therapeutics 59 23223830
2017 Effect of Modified Vaccinia Ankara-5T4 and Low-Dose Cyclophosphamide on Antitumor Immunity in Metastatic Colorectal Cancer: A Randomized Clinical Trial. JAMA oncology 58 28880972
2002 Attenuated recombinant vaccinia virus expressing oncofetal antigen (tumor-associated antigen) 5T4 induces active therapy of established tumors. Molecular cancer therapeutics 57 12481437
2018 Preclinical Assessment of CAR T-Cell Therapy Targeting the Tumor Antigen 5T4 in Ovarian Cancer. Journal of immunotherapy (Hagerstown, Md. : 1997) 52 29239915
2010 CXCR4 mediated chemotaxis is regulated by 5T4 oncofetal glycoprotein in mouse embryonic cells. PloS one 48 20376365
2007 A phase II study of a 5T4 oncofoetal antigen tumour-targeted superantigen (ABR-214936) therapy in patients with advanced renal cell carcinoma. British journal of cancer 47 17285137
2014 A priori prediction of tumor payload concentrations: preclinical case study with an auristatin-based anti-5T4 antibody-drug conjugate. The AAPS journal 46 24578215
2008 Vaccination of renal cell cancer patients with modified vaccinia ankara delivering tumor antigen 5T4 (TroVax) administered with interleukin 2: a phase II trial. Clinical cancer research : an official journal of the American Association for Cancer Research 46 19010868
2016 5T4-Targeted Therapy Ablates Cancer Stem Cells and Prevents Recurrence of Head and Neck Squamous Cell Carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 45 27780858
2005 Active treatment of murine tumors with a highly attenuated vaccinia virus expressing the tumor associated antigen 5T4 (TroVax) is CD4+ T cell dependent and antibody mediated. Cancer immunology, immunotherapy : CII 43 16311730
2002 5T4 interacts with TIP-2/GIPC, a PDZ protein, with implications for metastasis. Biochemical and biophysical research communications 42 11798178
1995 Metastasis-associated 5T4 oncofoetal antigen is concentrated at microvillus projections of the plasma membrane. Journal of cell science 42 7593330
1985 Right- and left-handed (Z) helical conformations of the hairpin d(C-G)5T4(C-G)5 monomer and dimer. Biochemistry 42 4084487
2003 The 5T4 oncofoetal antigen is an early differentiation marker of mouse ES cells and its absence is a useful means to assess pluripotency. Journal of cell science 41 14576347
1998 5T4 oncofetal antigen in gastric carcinoma and its clinical significance. European journal of gastroenterology & hepatology 41 9855063
2014 Structural insights into the inhibition of Wnt signaling by cancer antigen 5T4/Wnt-activated inhibitory factor 1. Structure (London, England : 1993) 40 24582434
2009 Vaccination of patients with metastatic renal cancer with modified vaccinia Ankara encoding the tumor antigen 5T4 (TroVax) given alongside interferon-alpha. Journal of immunotherapy (Hagerstown, Md. : 1997) 40 19342962
2008 An MVA-based vaccine targeting the oncofetal antigen 5T4 in patients undergoing surgical resection of colorectal cancer liver metastases. Journal of immunotherapy (Hagerstown, Md. : 1997) 39 18833005
2017 First-in-human trial of an anti-5T4 antibody-monomethylauristatin conjugate, PF-06263507, in patients with advanced solid tumors. Investigational new drugs 38 28070718
2017 Preclinical Evaluation of MEDI0641, a Pyrrolobenzodiazepine-Conjugated Antibody-Drug Conjugate Targeting 5T4. Molecular cancer therapeutics 38 28522587
2005 Embryonic expression of murine 5T4 oncofoetal antigen is associated with morphogenetic events at implantation and in developing epithelia. Developmental dynamics : an official publication of the American Association of Anatomists 38 15977177
2015 Cross-Presentation of the Oncofetal Tumor Antigen 5T4 from Irradiated Prostate Cancer Cells--A Key Role for Heat-Shock Protein 70 and Receptor CD91. Cancer immunology research 36 25678582
2012 5T4 glycoprotein regulates the sensory input-dependent development of a specific subtype of newborn interneurons in the mouse olfactory bulb. The Journal of neuroscience : the official journal of the Society for Neuroscience 36 22323733
2020 Safety and immunogenicity of novel 5T4 viral vectored vaccination regimens in early stage prostate cancer: a phase I clinical trial. Journal for immunotherapy of cancer 34 32591433
2012 CXCL12 receptor preference, signal transduction, biological response and the expression of 5T4 oncofoetal glycoprotein. Journal of cell science 34 22956548
1999 Organisation of the mouse and human 5T4 oncofoetal leucine-rich glycoprotein genes and expression in foetal and adult murine tissues. Biochimica et biophysica acta 32 10366710
2017 5T4-specific chimeric antigen receptor modification promotes the immune efficacy of cytokine-induced killer cells against nasopharyngeal carcinoma stem cell-like cells. Scientific reports 31 28687750
1988 Comparison of the B- and Z-form hairpin loop structures formed by d(CG)5T4(CG)5. Biochemistry 31 3196693
2012 Overexpression and potential targeting of the oncofoetal antigen 5T4 in malignant pleural mesothelioma. Lung cancer (Amsterdam, Netherlands) 29 22498111
2008 The oncofetal protein, 5T4, is a suitable target for antibody-guided anti-cancer chemotherapy with calicheamicin. International journal of oncology 29 18097562
2012 5T4 oncofetal antigen is expressed in high risk of relapse childhood pre-B acute lymphoblastic leukemia and is associated with a more invasive and chemotactic phenotype. Leukemia 27 22266911
2017 5T4 oncofoetal glycoprotein: an old target for a novel prostate cancer immunotherapy. Oncotarget 25 28537896
1990 Investigation of expression of 5T4 antigen in cervical cancer. British journal of cancer 25 2404512
2000 Isolation of a high affinity scFv from a monoclonal antibody recognising the oncofoetal antigen 5T4. Biochimica et biophysica acta 24 11113573
2021 ASN004, A 5T4-targeting scFv-Fc Antibody-Drug Conjugate with High Drug-to-Antibody Ratio, Induces Complete and Durable Tumor Regressions in Preclinical Models. Molecular cancer therapeutics 23 34045226
2010 TroVax, a recombinant modified vaccinia Ankara virus encoding 5T4: lessons learned and future development. Human vaccines 22 20975327
2009 Immune evasion mechanisms in colorectal cancer liver metastasis patients vaccinated with TroVax (MVA-5T4). Cancer immunology, immunotherapy : CII 22 19221742
2006 CD8 T-cell recognition of human 5T4 oncofetal antigen. International journal of cancer 22 16646078
2019 Preclinical development of T-cell receptor-engineered T-cell therapy targeting the 5T4 tumor antigen on renal cell carcinoma. Cancer immunology, immunotherapy : CII 20 31686124
2017 Trophoblast Glycoprotein (TPGB/5T4) in Human Placenta: Expression, Regulation, and Presence in Extracellular Microvesicles and Exosomes. Reproductive sciences (Thousand Oaks, Calif.) 20 28481180
2012 Analysis of pre-treatment markers predictive of treatment benefit for the therapeutic cancer vaccine MVA-5T4 (TroVax). Cancer immunology, immunotherapy : CII 20 22692758
2002 Characterization of the murine 5T4 oncofoetal antigen: a target for immunotherapy in cancer. The Biochemical journal 20 12003637
2019 Antitumor activity of a 5T4 targeting antibody drug conjugate with a novel payload derived from MMAF via C-Lock linker. Cancer medicine 19 30843650
2018 A novel 5T4-targeting antibody-drug conjugate H6-DM4 exhibits potent therapeutic efficacy in gastrointestinal tumor xenograft models. American journal of cancer research 19 29736307
2006 Cell surface 5T4 antigen is transiently upregulated during early human embryonic stem cell differentiation: effect of 5T4 phenotype on neural lineage formation. Experimental cell research 19 16616918
2015 Enhanced Antitumor Activity of an Anti-5T4 Antibody-Drug Conjugate in Combination with PI3K/mTOR inhibitors or Taxanes. Clinical cancer research : an official journal of the American Association for Cancer Research 18 26319086
2013 Escalating regulation of 5T4-specific IFN-γ+ CD4+ T cells distinguishes colorectal cancer patients from healthy controls and provides a target for in vivo therapy. Cancer immunology research 18 24409450
2002 Glycosylation and epitope mapping of the 5T4 glycoprotein oncofoetal antigen. The Biochemical journal 18 11903056
2020 Effective antitumor activity of 5T4-specific CAR-T cells against ovarian cancer cells in vitro and xenotransplanted tumors in vivo. MedComm 17 34766126
2019 Cancer stem cell mobilization and therapeutic targeting of the 5T4 oncofetal antigen. Therapeutic advances in vaccines and immunotherapy 17 30719508
2007 CD4+ T-cell recognition of human 5T4 oncofoetal antigen: implications for initial depletion of CD25+ T cells. Cancer immunology, immunotherapy : CII 17 18004564
2006 Identification of a major histocompatibility complex class I-restricted T-cell epitope in the tumour-associated antigen, 5T4. Immunology 17 16630022
2019 Role of TPBG (Trophoblast Glycoprotein) Antigen in Human Pericyte Migratory and Angiogenic Activity. Arteriosclerosis, thrombosis, and vascular biology 15 31018661
2002 Targeting immune effector molecules to human tumor cells through genetic delivery of 5T4-specific scFv fusion proteins. Cancer gene therapy 15 12386827
2010 5T4-modified vaccinia Ankara: progress in tumor-associated antigen-based immunotherapy. Expert opinion on biological therapy 13 20088718
2008 Development of modified vaccinia Ankara-5T4 as specific immunotherapy for advanced human cancer. Expert opinion on biological therapy 13 18990081
2001 The pattern of expression of the 5T4 oncofoetal antigen on normal, dysplastic and malignant oral mucosa. Oral oncology 13 11120484
1990 Trophoblast glycoprotein recognised by monoclonal antibody 5T4 maps to human chromosome 6q14-q15. Human genetics 13 2323778
2018 The nature of the human T cell response to the cancer antigen 5T4 is determined by the balance of regulatory and inflammatory T cells of the same antigen-specificity: implications for vaccine design. Cancer immunology, immunotherapy : CII 12 30406375
2022 LINC00342 induces metastasis of lung adenocarcinoma by targeting miR-15b/TPBG. Acta biochimica Polonica 10 35452205
2018 The 5T4 oncofetal glycoprotein does not act as a general organizer of the CXCL12 system in cancer cells. Experimental cell research 10 29408206
2023 The Bispecific Tumor Antigen-Conditional 4-1BB x 5T4 Agonist, ALG.APV-527, Mediates Strong T-Cell Activation and Potent Antitumor Activity in Preclinical Studies. Molecular cancer therapeutics 9 36343381
2014 Control of established colon cancer xenografts using a novel humanized single chain antibody-streptococcal superantigen fusion protein targeting the 5T4 oncofetal antigen. PloS one 9 24736661
2012 CD8+ T-cell clones specific for the 5T4 antigen target renal cell carcinoma tumor-initiating cells in a murine xenograft model. Journal of immunotherapy (Hagerstown, Md. : 1997) 9 22892449
2011 Regulation of autologous immunity to the mouse 5T4 oncofoetal antigen: implications for immunotherapy. Cancer immunology, immunotherapy : CII 9 22127365
2019 Combination Treatment with an Antibody-Drug Conjugate (A1mcMMAF) Targeting the Oncofetal Glycoprotein 5T4 and Carboplatin Improves Survival in a Xenograft Model of Ovarian Cancer. Targeted oncology 8 31332693
2017 Targeting the 5T4 oncofetal glycoprotein with an antibody drug conjugate (A1mcMMAF) improves survival in patient-derived xenograft models of acute lymphoblastic leukemia. Haematologica 8 28341731
2017 Detecting expression of 5T4 in CTCs and tumor samples from NSCLC patients. PloS one 8 28727782
2025 Targeting Tumor Antigen 5T4 Using CAR T Cells for the Treatment of Acute Myeloid Leukemia. Molecular cancer therapeutics 7 39387839
2025 Enhancing the potency of 5T4 mRNA vaccine by CD70 mRNA-LNPs through ADCC and T cell boosting in prostate cancer therapy. Journal of nanobiotechnology 7 40676580
2014 Phenotype of TPBG Gene Replacement in the Mouse and Impact on the Pharmacokinetics of an Antibody-Drug Conjugate. Molecular pharmaceutics 7 25423493
2007 5T4-modified vaccinia ankara: progress in tumor-associated antigen-based immunotherapy. Expert opinion on biological therapy 7 17727334
2025 Tri-specific tribodies targeting 5T4, CD3, and immune checkpoint drive stronger functional T-cell responses than combinations of antibody therapeutics. Cell death discovery 6 39929828
2024 A randomized phase II trial to examine modified vaccinia Ankara-5T4 vaccine in patients with relapsed asymptomatic ovarian cancer (TRIOC). International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 5 38760075
2013 Identification of Pre- and Post-Treatment Markers, Clinical, and Laboratory Parameters Associated with Outcome in Renal Cancer Patients Treated with MVA-5T4. Frontiers in oncology 5 23875174
2022 Identification of TPBG-Expressing Amacrine Cells in DAT-tdTomato Mouse. Investigative ophthalmology & visual science 4 35551574
2020 LRR-Containing Oncofetal Trophoblast Glycoprotein 5T4 Shapes Neural Circuits in Olfactory and Visual Systems. Frontiers in molecular neuroscience 4 33192298
2019 Expression of Oncofetal Antigen 5T4 in Murine Taste Papillae. Frontiers in cellular neuroscience 4 31417363
2018 The breast cancer antigen 5T4 interacts with Rab11, and is a target and regulator of Rab11 mediated trafficking. The international journal of biochemistry & cell biology 4 29549047
2013 Murine responses to recombinant MVA versus ALVAC vaccines against tumor-associated antigens, gp100 and 5T4. Journal of immunotherapy (Hagerstown, Md. : 1997) 4 23603858
2007 Novel vectors for homologous recombination strategies in mouse embryonic stem cells: an ES cell line expressing EGFP under control of the 5T4 promoter. Experimental cell research 4 17765223
2024 Preclinical evaluation and pilot clinical study of [68Ga]Ga-NOTA-H006 for non-invasive PET imaging of 5T4 oncofetal antigen. European journal of nuclear medicine and molecular imaging 3 39377811
2007 5T4 oncotrophoblast glycoprotein: janus molecule in life and a novel potential target against tumors. Cellular & molecular immunology 3 17484803
2025 Development of [18F]AlF-RESCA-H006 as a Novel Molecular Probe for 5T4 Tumor Imaging and Exploration of Its Application in Pancreatic Adenocarcinoma. Molecular pharmaceutics 2 40443260
2025 Preclinical Characterization of XB010: A Novel Antibody-Drug Conjugate for the Treatment of Solid Tumors that Targets Tumor-Associated Antigen 5T4. Molecular cancer therapeutics 2 40836888

Missed literature

Know a paper Affinage missed for TPBG? Flag it for the maintainers and the community.

No submissions yet.