TPBG

Summary

Gene Symbol: TPBG
Description: trophoblast glycoprotein
Alias: 5T4, 5T4AG, M6P1, WAIF1, trophoblast glycoprotein, 5T4 oncofetal antigen, 5T4 oncofetal trophoblast glycoprotein, 5T4 oncotrophoblast glycoprotein, wnt-activated inhibitory factor 1
Species: human
Products:     TPBG

Top Publications

  1. Carsberg C, Myers K, Evans G, Allen T, Stern P. Metastasis-associated 5T4 oncofoetal antigen is concentrated at microvillus projections of the plasma membrane. J Cell Sci. 1995;108 ( Pt 8):2905-16 pubmed
    The 5T4 oncofoetal antigen is a 72 kDa glycoprotein defined by a monoclonal antibody raised against human placental trophoblast and is expressed in many different carcinomas but detected only at low levels in some normal epithelia...
  2. Myers K, Rahi Saund V, Davison M, Young J, Cheater A, Stern P. Isolation of a cDNA encoding 5T4 oncofetal trophoblast glycoprotein. An antigen associated with metastasis contains leucine-rich repeats. J Biol Chem. 1994;269:9319-24 pubmed
    The monoclonal antibody 5T4 defines a human oncotrophoblast antigen expressed by a variety of carcinomas but with a restricted pattern of expression in normal adult tissues...
  3. Mulryan K, Ryan M, Myers K, Shaw D, Wang W, Kingsman S, et al. Attenuated recombinant vaccinia virus expressing oncofetal antigen (tumor-associated antigen) 5T4 induces active therapy of established tumors. Mol Cancer Ther. 2002;1:1129-37 pubmed
    The human oncofetal antigen 5T4 (h5T4) is a transmembrane glycoprotein overexpressed by a wide spectrum of cancers, including colorectal, ovarian, and gastric, but with a limited normal tissue expression...
  4. Awan A, Lucic M, Shaw D, Sheppard F, Westwater C, Lyons S, et al. 5T4 interacts with TIP-2/GIPC, a PDZ protein, with implications for metastasis. Biochem Biophys Res Commun. 2002;290:1030-6 pubmed
    Overexpression of the 5T4 transmembrane glycoprotein can have marked effects on both the actin cytoskeleton and cell migration...
  5. Kagermeier Schenk B, Wehner D, Ozhan Kizil G, Yamamoto H, Li J, Kirchner K, et al. Waif1/5T4 inhibits Wnt/β-catenin signaling and activates noncanonical Wnt pathways by modifying LRP6 subcellular localization. Dev Cell. 2011;21:1129-43 pubmed publisher
    ..Here we show that the metastasis-associated transmembrane protein Wnt-activated inhibitory factor 1 (Waif1/5T4) interferes with Wnt/β-catenin signaling and concomitantly activates noncanonical Wnt pathways...
  6. Papachristofilou A, Hipp M, Klinkhardt U, Fruh M, Sebastian M, Weiss C, et al. Phase Ib evaluation of a self-adjuvanted protamine formulated mRNA-based active cancer immunotherapy, BI1361849 (CV9202), combined with local radiation treatment in patients with stage IV non-small cell lung cancer. J Immunother Cancer. 2019;7:38 pubmed publisher
    ..mRNA encoding six non-small cell lung cancer (NSCLC)-associated antigens (NY-ESO-1, MAGE-C1, MAGE-C2, survivin, 5T4, and MUC-1), intended to induce targeted immune responses...
  7. Liu X, Wang J, Chen M, Liu S, Yu X, Wen F. Combining data from TCGA and GEO databases and reverse transcription quantitative PCR validation to identify gene prognostic markers in lung cancer. Onco Targets Ther. 2019;12:709-720 pubmed publisher
    ..Five markers of gene composition (ribonucleotide reductase regulatory subunit M2 [RRM2], trophoblast glycoprotein [TPBG], transmembrane protease serine 4[TMPRFF4], chloride intracellular channel 3 [CLIC3], and WNT ..
  8. Besneux M, Greenshields Watson A, Scurr M, MacLachlan B, Christian A, Davies M, et al. 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 Immunol Immunother. 2019;68:247-256 pubmed publisher
    The oncofoetal antigen 5T4 is a promising T cell target in the context of colorectal cancer, as demonstrated by a recent clinical study where 5T4-specific T cell responses, induced by vaccination or cyclophosphamide, were associated with ..
  9. Zhong H, Chen C, Tammali R, Breen S, Zhang J, Fazenbaker C, et al. Improved Therapeutic Window in BRCA-mutant Tumors with Antibody-linked Pyrrolobenzodiazepine Dimers with and without PARP Inhibition. Mol Cancer Ther. 2018;: pubmed publisher
    ..To support this hypothesis, we found 5T4-PBD, a PBD-dimer conjugated to anti-5T4 antibody, elicited more potent antitumor activity in tumor xenografts that ..

More Information

Publications47

  1. Damelin M, Zhong W, Myers J, Sapra P. Evolving Strategies for Target Selection for Antibody-Drug Conjugates. Pharm Res. 2015;32:3494-507 pubmed publisher
    ..The TPBG (5T4) oncofetal antigen and the anti-TPBG ADC A1-mcMMAF are highlighted to demonstrate the relevance of the target'..
  2. Schunselaar L, Monkhorst K, van der Noort V, Wijdeven R, Peters D, Zwart W, et al. Trophoblast Glycoprotein is Associated With a Favorable Outcome for Mesothelioma and a Target for Antibody Drug Conjugates. J Thorac Oncol. 2018;13:1577-1587 pubmed publisher
    ..Antibody drug conjugates (ADCs) are gaining interest as a therapeutic strategy in mesothelioma. Trophoblast glycoprotein (5T4) is an oncofetal protein overexpressed in mesothelioma with low expression in normal tissue and ..
  3. Salimu J, Spary L, Al Taei S, Clayton A, Mason M, Staffurth J, et al. 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 Immunol Res. 2015;3:678-88 pubmed publisher
    ..We established a cross-presentation model in which DCs present a naturally expressed oncofetal tumor antigen (5T4) from irradiated DU145 prostate cancer cells to 5T4-specific T cells...
  4. Wang R, Lai Q, Lu Y, Zhou Y, Tang L, Tao Y, et al. Expression of 5T4 extracellular domain fusion protein and preparation of anti-5T4 monoclonal antibody with high affinity and internalization efficiency. Protein Expr Purif. 2018;158:51-58 pubmed publisher
    b>5T4, a membrane protein, is overexpressed in many tumor tissues but rarely expressed in normal tissues. Here, CHO-5T4+ cells were generated and served as the antigen to immunize mice...
  5. Malinauskas T, Jones E. Extracellular modulators of Wnt signalling. Curr Opin Struct Biol. 2014;29:77-84 pubmed publisher
    ..extracellular fragments of Wnt co-receptor LRP6, LRP6-binding antagonists Dickkopf and Sclerostin, antagonists 5T4/WAIF1 and Wnt inhibitory factor 1 (WIF-1), as well as Frizzled-ubiquitin ligases ZNRF3/RNF43 (in isolation and in ..
  6. Spencer H, Eastham A, Merry C, Southgate T, Perez Campo F, Soncin F, et al. E-cadherin inhibits cell surface localization of the pro-migratory 5T4 oncofetal antigen in mouse embryonic stem cells. Mol Biol Cell. 2007;18:2838-51 pubmed
    ..The 5T4 oncofetal antigen, previously shown to be associated with very early ES cell differentiation and altered motility, is also a ..
  7. Li Q, White J, Peterson N, Rickert K, Lloyd C, Allen K, et al. Tumor uptake of pegylated diabodies: Balancing systemic clearance and vascular transport. J Control Release. 2018;279:126-135 pubmed publisher
    ..In this study, we use a diabody, the dimeric antibody fragment, targeting the 5T4 antigen to assess the impact of PEGs of distinct size and shape on tumor accumulation and pharmacokinetics (PK)...
  8. Stern P, Harrop R. 5T4 oncofoetal antigen: an attractive target for immune intervention in cancer. Cancer Immunol Immunother. 2017;66:415-426 pubmed publisher
    ..The 5T4 oncofoetal antigen was identified by searching for surface molecules shared between human trophoblast and cancer ..
  9. Singh A, Winslow T, Kermany M, Goritz V, Heit L, Miller A, et al. A Pilot Study of Stereotactic Body Radiation Therapy Combined with Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma. Clin Cancer Res. 2017;23:5055-5065 pubmed publisher
    ..SBRT-treated tumors had increased expression of the immunomodulatory molecule calreticulin and TAA (CA9, 5T4, NY-ESO-1, and MUC-1)...
  10. Harris J, Dave K, Gorman J, Khanna K. The breast cancer antigen 5T4 interacts with Rab11, and is a target and regulator of Rab11 mediated trafficking. Int J Biochem Cell Biol. 2018;99:28-37 pubmed publisher
    b>5T4 is a transmembrane glycoprotein with limited expression in normal adult tissues and expression in some solid tumours. It is unclear whether 5T4 is preferentially expressed by stem or differentiated cell types...
  11. Clarke S, Betts G, Plant A, Wright K, El Shanawany T, Harrop R, et al. CD4+CD25+FOXP3+ regulatory T cells suppress anti-tumor immune responses in patients with colorectal cancer. PLoS ONE. 2006;1:e129 pubmed
    ..of CRC patients unmasked CD4(+) T cell responses, as observed by IFNgamma release, to the tumor associated antigen 5T4, whereas no effect was observed in a healthy age-matched control group...
  12. Harper J, Lloyd C, Dimasi N, Toader D, Marwood R, Lewis L, et al. Preclinical Evaluation of MEDI0641, a Pyrrolobenzodiazepine-Conjugated Antibody-Drug Conjugate Targeting 5T4. Mol Cancer Ther. 2017;16:1576-1587 pubmed publisher
    ..b>5T4 is an oncofetal antigen overexpressed on the cell surface in many carcinomas on both bulk tumor cells as well as ..
  13. Shor B, Kahler J, Dougher M, Xu J, Mack M, Rosfjord E, et al. Enhanced Antitumor Activity of an Anti-5T4 Antibody-Drug Conjugate in Combination with PI3K/mTOR inhibitors or Taxanes. Clin Cancer Res. 2016;22:383-94 pubmed publisher
    ..An auristatin-based anti-5T4 antibody conjugate (5T4-ADC) and auristatin payloads were combined with the dual PI3K/mTOR catalytic site inhibitor ..
  14. Giddabasappa A, Gupta V, Norberg R, Gupta P, Spilker M, Wentland J, et al. Biodistribution and Targeting of Anti-5T4 Antibody-Drug Conjugate Using Fluorescence Molecular Tomography. Mol Cancer Ther. 2016;15:2530-2540 pubmed
    ..An anti-5T4-antibody (5T4-Ab) and 5T4-ADC were conjugated with a near-infrared (NIR) fluorophore VivoTag 680XL (VT680)...
  15. Puchert M, Koch C, Engele J. The 5T4 oncofetal glycoprotein does not act as a general organizer of the CXCL12 system in cancer cells. Exp Cell Res. 2018;364:175-183 pubmed publisher
    ..Since it has been previously suggested that the cellular use of CXCR4 or CXCR7 is dictated by the 5T4 oncofetal glycoprotein, we have now tested whether 5T4 would represent a general and reliable marker for the ..
  16. McGinn O, Krishnan S, Bourquin J, Sapra P, Dempsey C, Saha V, et al. Targeting the 5T4 oncofetal glycoprotein with an antibody drug conjugate (A1mcMMAF) improves survival in patient-derived xenograft models of acute lymphoblastic leukemia. Haematologica. 2017;102:1075-1084 pubmed publisher
    ..Here we identify high expression of 5T4 in subclonal populations of patient-derived xenografts from patients with high, post-induction levels of minimal ..
  17. Shapiro G, Vaishampayan U, LoRusso P, Barton J, Hua S, Reich S, et al. First-in-human trial of an anti-5T4 antibody-monomethylauristatin conjugate, PF-06263507, in patients with advanced solid tumors. Invest New Drugs. 2017;35:315-323 pubmed publisher
    Background The antibody-drug conjugate PF-06263507 targets the cell-surface, tumor-associated antigen 5T4 and consists of a humanized IgG1 conjugated to the microtubule-disrupting agent monomethylauristatin-F by a non-cleavable ..
  18. Guo X, Zheng H, Luo W, Zhang Q, Liu J, Yao K. 5T4-specific chimeric antigen receptor modification promotes the immune efficacy of cytokine-induced killer cells against nasopharyngeal carcinoma stem cell-like cells. Sci Rep. 2017;7:4859 pubmed publisher
    ..By investigating the expression patterns of potential target antigens (ROR1, 5T4 and CAIX) in NPC, we found that the oncofetal antigen 5T4 was predominately expressed in NPC cell lines and tissues ..
  19. Takahashi H, Ogawa Y, Yoshihara S, Asahina R, Kinoshita M, Kitano T, et al. A Subtype of Olfactory Bulb Interneurons Is Required for Odor Detection and Discrimination Behaviors. J Neurosci. 2016;36:8210-27 pubmed publisher
    ..Here, we investigated the in vivo functional role of oncofetal trophoblast glycoprotein 5T4, a regulator for dendritic arborization of 5T4-expressing GCs (5T4 GCs), the level of which is ..
  20. Kloudova K, Hromádková H, Partlová S, Brtnický T, Rob L, Bartunkova J, et al. Expression of tumor antigens on primary ovarian cancer cells compared to established ovarian cancer cell lines. Oncotarget. 2016;7:46120-46126 pubmed publisher
    ..FOLR1, Her-2/neu, MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A10, MAGE-A12, MUC-1, NY-ESO-1, PRAME, p53, TPBG, TRT, WT1) in 4 established ovarian cancer cell lines and in primary tumor cells isolated from the high-grade ..
  21. Shaw D, Woods A, Myers K, Westwater C, Rahi Saund V, Davies M, et al. Glycosylation and epitope mapping of the 5T4 glycoprotein oncofoetal antigen. Biochem J. 2002;363:137-45 pubmed
    The human 5T4 oncofoetal antigen is a focus for development of several antibody-directed therapies on the basis of the murine monoclonal antibody against 5T4 (mAb5T4), which recognizes a conformational epitope...
  22. Jun G, Chung J, Mez J, Barber R, Beecham G, Bennett D, et al. Transethnic genome-wide scan identifies novel Alzheimer's disease loci. Alzheimers Dement. 2017;13:727-738 pubmed publisher
    ..7 × 10-6) for gene-based association in the total sample with a novel locus, TPBG (P = 1.8 × 10-6)...
  23. Shingler W, Chikoti P, Kingsman S, Harrop R. Identification and functional validation of MHC class I epitopes in the tumor-associated antigen 5T4. Int Immunol. 2008;20:1057-66 pubmed publisher
    The cancer vaccine TroVax, modified vaccinia Ankara encoding the tumor-associated antigen 5T4, has been tested in phase I and II studies in colorectal cancer patients...
  24. McGinn O, Marinov G, Sawan S, Stern P. CXCL12 receptor preference, signal transduction, biological response and the expression of 5T4 oncofoetal glycoprotein. J Cell Sci. 2012;125:5467-78 pubmed publisher
    ..We have recently demonstrated that 5T4 oncofoetal glycoprotein facilitates functional CXCR4 expression leading to CXCL12 mediated chemotaxis in mouse ..
  25. Owens G, Sheard V, Kalaitsidou M, Blount D, Lad Y, Cheadle E, et al. Preclinical Assessment of CAR T-Cell Therapy Targeting the Tumor Antigen 5T4 in Ovarian Cancer. J Immunother. 2017;: pubmed publisher
    ..The 5T4 is a tumor-associated antigen which is expressed on the cell surface of most solid tumors including ovarian cancer...
  26. King K, Sheppard F, Westwater C, Stern P, Myers K. Organisation of the mouse and human 5T4 oncofoetal leucine-rich glycoprotein genes and expression in foetal and adult murine tissues. Biochim Biophys Acta. 1999;1445:257-70 pubmed
    The human 5T4 oncotrophoblast leucine-rich glycoprotein may contribute to the process of placentation or metastasis by modulating cell adhesion, shape and motility...
  27. Kerk S, Finkel K, Pearson A, Warner K, Zhang Z, Nör F, et al. 5T4-Targeted Therapy Ablates Cancer Stem Cells and Prevents Recurrence of Head and Neck Squamous Cell Carcinoma. Clin Cancer Res. 2017;23:2516-2527 pubmed publisher
    ..Design: Here, we evaluated the efficacy of MEDI0641, a novel antibody-drug conjugate targeted to 5T4 and carrying a DNA-damaging "payload" (pyrrolobenzodiazepine) in preclinical models of HNSCC...
  28. Stern P, Brazzatti J, Sawan S, McGinn O. Understanding and exploiting 5T4 oncofoetal glycoprotein expression. Semin Cancer Biol. 2014;29:13-20 pubmed publisher
    ..The 5T4 oncofoetal glycoprotein was identified by searching for shared surface molecules of human trophoblast and cancer ..
  29. Al Taei S, Salimu J, Lester J, Linnane S, Goonewardena M, Harrop R, et al. Overexpression and potential targeting of the oncofoetal antigen 5T4 in malignant pleural mesothelioma. Lung Cancer. 2012;77:312-8 pubmed publisher
    ..The aim of this study was to evaluate the level of expression and the relevance of 5T4 as a tumour-associated antigen in MPM...
  30. Carsberg C, Myers K, Stern P. Metastasis-associated 5T4 antigen disrupts cell-cell contacts and induces cellular motility in epithelial cells. Int J Cancer. 1996;68:84-92 pubmed
    The 5T4 antigen is defined by a monoclonal antibody (MAb) specific for human trophoblast. It is also expressed by many types of tumour cell and has been associated with metastasis and poor clinical outcome in a number of cancers...
  31. Elkord E, Dangoor A, Drury N, Harrop R, Burt D, Drijfhout J, et al. An MVA-based vaccine targeting the oncofetal antigen 5T4 in patients undergoing surgical resection of colorectal cancer liver metastases. J Immunother. 2008;31:820-9 pubmed publisher
    ..Blood was taken at trial entry and 2 weeks after each vaccination; tumor biopsies were collected at surgery. 5T4-specific cellular responses were assessed by lymphocyte proliferation and enzyme-linked immunosorbent spot, with ..
  32. Hasegawa Ishii S, Shimada A, Imamura F. Lipopolysaccharide-initiated persistent rhinitis causes gliosis and synaptic loss in the olfactory bulb. Sci Rep. 2017;7:11605 pubmed publisher
    ..cells, vesicular glutamate transporter 1, a presynaptic protein, in mitral and tufted projection neurons, and 5T4 in granule cells...
  33. Abdalla Z, Walsh T, Thakker N, Ward C. Loss of epithelial markers is an early event in oral dysplasia and is observed within the safety margin of dysplastic and T1 OSCC biopsies. PLoS ONE. 2017;12:e0187449 pubmed publisher
    ..Here we have assessed expression of the oral epithelial markers E-cadherin, EMP1 and 5T4 and the pro-invasive N-cadherin proteins using fully characterised antibodies and quantitative immunofluorescence ..
  34. He P, Jiang S, Ma M, Wang Y, Li R, Fang F, et al. Trophoblast glycoprotein promotes pancreatic ductal adenocarcinoma cell metastasis through Wnt/planar cell polarity signaling. Mol Med Rep. 2015;12:503-9 pubmed publisher
    b>Trophoblast glycoprotein (TPBG), a 72 kDa glycoprotein was identified using a monoclonal antibody, which specifically binds human trophoblast...
  35. Zhao Y, Malinauskas T, Harlos K, Jones E. Structural insights into the inhibition of Wnt signaling by cancer antigen 5T4/Wnt-activated inhibitory factor 1. Structure. 2014;22:612-20 pubmed publisher
    The tumor antigen 5T4/WAIF1 (Wnt-activated inhibitory factor 1; also known as Trophoblast glycoprotein TPBG) is a cell surface protein targeted in multiple cancer immunotherapy clinical trials...
  36. Ward C, Eastham A, Stern P. Cell surface 5T4 antigen is transiently upregulated during early human embryonic stem cell differentiation: effect of 5T4 phenotype on neural lineage formation. Exp Cell Res. 2006;312:1713-26 pubmed
    The 5T4 oncofoetal antigen is a cell surface glycoprotein that is transiently expressed during mouse ES cell differentiation and correlates with decreased pluripotency of such cells...
  37. Okazaki S, Sekizawa A, Purwosunu Y, Farina A, Wibowo N, Okai T. Placenta-derived, cellular messenger RNA expression in the maternal blood of preeclamptic women. Obstet Gynecol. 2007;110:1130-6 pubmed
    ..Both pregnancy-specific beta1 glycoprotein and trophoblast glycoprotein were selected based on microarray analysis...
  38. Smyth L, Elkord E, Taher T, Jiang H, Burt D, Clayton A, et al. CD8 T-cell recognition of human 5T4 oncofetal antigen. Int J Cancer. 2006;119:1638-47 pubmed
    The 5T4 oncofetal antigen is expressed by a wide variety of human carcinomas, including colorectal, ovarian and gastric carcinomas...