Target Information
| Target General Information | Top | |||||
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| Target ID |
T16601
(Former ID: TTDR00681)
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| Target Name |
Carcinoembryonic antigen CEA (CD66e)
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| Synonyms |
Meconium antigen 100; Carcinoembryonic antigen-related cell adhesion molecule 5; CEA; CD66e antigen
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| Gene Name |
CEACAM5
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Lung cancer [ICD-11: 2C25] | |||||
| 2 | Non-small-cell lung cancer [ICD-11: 2C25] | |||||
| Function |
Mediates homophilic and heterophilic cell adhesion with other carcinoembryonic antigen-related cell adhesion molecules, such as CEACAM6. Plays a role as an oncogene by promoting tumor progression; induces resistance to anoikis of colorectal carcinoma cells. Cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression.
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| BioChemical Class |
Immunoglobulin
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| UniProt ID | ||||||
| Sequence |
MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQ
HLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFY TLHVIKSDLVNEEATGQFRVYPELPKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWV NNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYKCETQNPVSARRSDSVILNVLYGPDAP TISPLNTSYRSGENLNLSCHAASNPPAQYSWFVNGTFQQSTQELFIPNITVNNSGSYTCQ AHNSDTGLNRTTVTTITVYAEPPKPFITSNNSNPVEDEDAVALTCEPEIQNTTYLWWVNN QSLPVSPRLQLSNDNRTLTLLSVTRNDVGPYECGIQNKLSVDHSDPVILNVLYGPDDPTI SPSYTYYRPGVNLSLSCHAASNPPAQYSWLIDGNIQQHTQELFISNITEKNSGLYTCQAN NSASGHSRTTVKTITVSAELPKPSISSNNSKPVEDKDAVAFTCEPEAQNTTYLWWVNGQS LPVSPRLQLSNGNRTLTLFNVTRNDARAYVCGIQNSVSANRSDPVTLDVLYGPDTPIISP PDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAKITPNNNGTYACFVSNL ATGRNNSIVKSITVSASGTSPGLSAGATVGIMIGVLVGVALI Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 23 Clinical Trial Drugs | + | ||||
| 1 | SAR408701 | Drug Info | Phase 3 | Non-small-cell lung cancer | [2] | |
| 2 | Tusamitamab ravtansine | Drug Info | Phase 3 | Non-small-cell lung cancer | [3] | |
| 3 | CAP1-6D | Drug Info | Phase 2 | Pancreatic cancer | [4] | |
| 4 | CeaVac | Drug Info | Phase 2 | Colorectal cancer | [5] | |
| 5 | GI-6207 | Drug Info | Phase 2 | Thyroid cancer | [6], [7] | |
| 6 | IDM-2101 | Drug Info | Phase 2 | Colorectal cancer | [8] | |
| 7 | Labetuzumab I-131 | Drug Info | Phase 2 | Colorectal cancer | [9] | |
| 8 | Pentacea | Drug Info | Phase 2 | Small-cell lung cancer | [10] | |
| 9 | AVX701 | Drug Info | Phase 1/2 | Colorectal cancer | [11] | |
| 10 | BDC-1001 | Drug Info | Phase 1/2 | Solid tumour/cancer | [12] | |
| 11 | CAR-T cells targeting CEA | Drug Info | Phase 1/2 | Colorectal cancer | [13] | |
| 12 | CT84.66 | Drug Info | Phase 1/2 | Breast cancer | [14] | |
| 13 | 123-Iodine-labeled MFE-23 | Drug Info | Phase 1 | Solid tumour/cancer | [15] | |
| 14 | AMG 211 | Drug Info | Phase 1 | Solid tumour/cancer | [7] | |
| 15 | Anti-CEA CAR-T cells | Drug Info | Phase 1 | Acute myeloid leukaemia | [16], [17] | |
| 16 | Anti-CEA CAR-T cells | Drug Info | Phase 1 | Colorectal cancer | [18] | |
| 17 | Anti-CEA-CAR T | Drug Info | Phase 1 | Colorectal cancer | [19] | |
| 18 | CAR-T Cells targeting CEA | Drug Info | Phase 1 | Pancreatic cancer | [20] | |
| 19 | CEA CAR-T | Drug Info | Phase 1 | Ascites | [21] | |
| 20 | CIGB-M3 | Drug Info | Phase 1 | Colorectal cancer | [22] | |
| 21 | MV-CEA | Drug Info | Phase 1 | Glioblastoma multiforme | [23] | |
| 22 | NEO-201 | Drug Info | Phase 1 | Solid tumour/cancer | [24] | |
| 23 | RG7813 | Drug Info | Phase 1 | Solid tumour/cancer | [25] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | KSB-303 | Drug Info | Discontinued in Phase 1/2 | Colorectal cancer | [26] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Modulator | [+] 4 Modulator drugs | + | ||||
| 1 | CAP1-6D | Drug Info | [1], [30] | |||
| 2 | GI-6207 | Drug Info | [32] | |||
| 3 | AVX701 | Drug Info | [36] | |||
| 4 | MV-CEA | Drug Info | [23] | |||
| CAR-T-Cell-Therapy | [+] 5 CAR-T-Cell-Therapy drugs | + | ||||
| 1 | CAR-T cells targeting CEA | Drug Info | [13] | |||
| 2 | Anti-CEA CAR-T cells | Drug Info | [16], [17] | |||
| 3 | Anti-CEA CAR-T cells | Drug Info | [18] | |||
| 4 | Anti-CEA-CAR T | Drug Info | [19] | |||
| 5 | CAR-T Cells targeting CEA | Drug Info | [20] | |||
| Immunomodulator | [+] 1 Immunomodulator drugs | + | ||||
| 1 | AMG 211 | Drug Info | [7] | |||
| Inhibitor | [+] 2 Inhibitor drugs | + | ||||
| 1 | NEO-201 | Drug Info | [40] | |||
| 2 | RG7813 | Drug Info | [28], [41] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: (1-Oxyl-2,2,5,5-tetramethylpyrroline-3-methyl)methanethiosulfonate | Ligand Info | |||||
| Structure Description | Structural model for the complex between the Dr adhesins and carcinoembryonic antigen (CEA) | PDB:2VER | ||||
| Method | Solution NMR | Resolution | N.A. | Mutation | No | [44] |
| PDB Sequence |
KLTIESTPFN
10 VAEGKEVLLL20 VHNLPQHLFG30 YSWYKGERCD40 GNCQIIGYVI50 GTQCATPGPA 60 YSGREIIYPN70 ASLLIQNIIQ80 NDTGFYTLHV90 IKSDLVNEEA100 TGQFRVYPEL 110
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Similarity Proteins
Human Tissue Distribution
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | TGF_beta_Receptor Signaling Pathway | |||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Identification of an enhancer agonist cytotoxic T lymphocyte peptide from human carcinoembryonic antigen. Cancer Res. 1997 Oct 15;57(20):4570-7. | |||||
| REF 2 | ClinicalTrials.gov (NCT04154956) SAR408701 Versus Docetaxel in Previously Treated, Carcinoembryonic Antigen-related Cell Adhesion Molecule 5 (CEACAM5) Positive Metastatic Non-squamous Non-small Cell Lung Cancer Patients (CARMEN-LC03). U.S. National Institutes of Health. | |||||
| REF 3 | ClinicalTrials.gov (NCT05245071) Open-label, Phase 2 Study, Evaluating the Efficacy and Safety of Tusamitamab Ravtansine in Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC) Participants With Negative or Moderate CEACAM5 Expression Tumors and High Circulating CEA. U.S.National Institutes of Health. | |||||
| REF 4 | ClinicalTrials.gov (NCT00203892) Study of CAP1-6D in Patients With Locally Advanced or Surgically Resected Pancreatic Adenocarcinoma. U.S. National Institutes of Health. | |||||
| REF 5 | ClinicalTrials.gov (NCT00003125) Vaccine Therapy, Interleukin-2, and Sargramostim in Treating Patients With Advanced Tumors. U.S. National Institutes of Health. | |||||
| REF 6 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 7 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 8 | Induction of immune responses and clinical efficacy in a phase II trial of IDM-2101, a 10-epitope cytotoxic T-lymphocyte vaccine, in metastatic non-small-cell lung cancer. J Clin Oncol. 2008 Sep 20;26(27):4418-25. | |||||
| REF 9 | Phase II trial of carcinoembryonic antigen radioimmunotherapy with 131I-labetuzumab after salvage resection of colorectal metastases in the liver: five-year safety and efficacy results. J Clin Oncol.2005 Sep 20;23(27):6763-70. | |||||
| REF 10 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800013510) | |||||
| REF 11 | ClinicalTrials.gov (NCT00529984) A Phase I/II Study With CEA(6D) VRP Vaccine in Patients With Advanced or Metastatic CEA-Expressing Malignancies. U.S. National Institutes of Health. | |||||
| REF 12 | ClinicalTrials.gov (NCT04278144) A First-in-human Study Using BDC-1001 in Advanced HER2-Expressing Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 13 | ClinicalTrials.gov (NCT02959151) A Study of Chimeric Antigen Receptor T Cells Combined With Interventional Therapy in Advanced Liver Malignancy | |||||
| REF 14 | ClinicalTrials.gov (NCT00645710) Hepatic Arterial Infusion of Floxuridine, Gemcitabine Hydrochloride, and Radiolabeled Monoclonal Antibody Therapy in Treating Liver Metastases in Patients With Metastatic Colorectal Cancer Previously Treated With Surgery. U.S. National Institutes of Health. | |||||
| REF 15 | A phase I trial of radioimmunotherapy with 131I-A5B7 anti-CEA antibody in combination with combretastatin-A4-phosphate in advanced gastrointestinal carcinomas. Clin Cancer Res. 2009 Jul 1;15(13):4484-92. | |||||
| REF 16 | ClinicalTrials.gov (NCT02416466) CAR-T Hepatic Artery Infusions and Sir-Spheres for Liver Metastases | |||||
| REF 17 | ClinicalTrials.gov (NCT02850536) CAR-T Hepatic Artery Infusions or Pancreatic Venous Infusions for CEA-Expressing Liver Metastases or Pancreas Cancer | |||||
| REF 18 | ClinicalTrials.gov (NCT03682744) CAR-T Intraperitoneal Infusions for CEA-Expressing Adenocarcinoma Peritoneal Metastases or Malignant Ascites (IPC) | |||||
| REF 19 | ClinicalTrials.gov (NCT02349724) A Clinical Research of CAR T Cells Targeting CEA Positive Cancer | |||||
| REF 20 | ClinicalTrials.gov (NCT03267173) Evaluate the Safety and Efficacy of CAR-T in the Treatment of Pancreatic Cancer. | |||||
| REF 21 | Clinical pipeline report, company report or official report of Sorrento Therapeutics. | |||||
| REF 22 | Phase I clinical trial of the (131)I-labeled anticarcinoembryonic antigen CIGB-M3 multivalent antibody fragment. Cancer Biother Radiopharm. 2011 Jun;26(3):353-63. | |||||
| REF 23 | Phase I trial of intraperitoneal administration of an oncolytic measles virus strain engineered to express carcinoembryonic antigen for recurrent ovarian cancer. Cancer Res. 2010 Feb 1;70(3):875-82. | |||||
| REF 24 | ClinicalTrials.gov (NCT03476681) QUILT-3.017: Study of NEO-201 in Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 25 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800039398) | |||||
| REF 26 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009269) | |||||
| REF 27 | ClinicalTrials.gov (NCT02187848) Evaluation of SAR408701 in Patients With Advanced Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 28 | Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36. | |||||
| REF 29 | Safety, pharmacokinetics, and antitumor activity of the anti-CEACAM5-DM4 antibody-drug conjugate tusamitamab ravtansine (SAR408701) in patients with advanced solid tumors: first-in-human dose-escalation study. Ann Oncol. 2022 Apr;33(4):416-425. | |||||
| REF 30 | HLA-A*0201-restricted CEA-derived peptide CAP1 is not a suitable target for T-cell-based immunotherapy. J Immunother. 2010 May;33(4):402-13. | |||||
| REF 31 | Clinical and immune responses in resected colon cancer patients treated with anti-idiotype monoclonal antibody vaccine that mimics the carcinoembryonic antigen. J Clin Oncol. 1999 Sep;17(9):2889-5. | |||||
| REF 32 | Clinical pipeline report, company report or official report of GlobeImmune. | |||||
| REF 33 | National Cancer Institute Drug Dictionary (drug id 692828). | |||||
| REF 34 | Clinical pipeline report, company report or official report of Immunomedics. | |||||
| REF 35 | Antibody fragments: Hope and hype. MAbs. 2010 Jan-Feb; 2(1): 77-83. | |||||
| REF 36 | Viral vector-based therapeutic cancer vaccines. Cancer J. 2011 Sep-Oct;17(5):359-71. | |||||
| REF 37 | Clinical pipeline report, company report or official report of Bolt Biotherapeutics. | |||||
| REF 38 | Technology evaluation: cT84.66, City of Hope. Curr Opin Mol Ther. 2004 Feb;6(1):90-5. | |||||
| REF 39 | Crystal structure of the anti-(carcinoembryonic antigen) single-chain Fv antibody MFE-23 and a model for antigen binding based on intermolecular contacts.. Biochem J. 2000 March 1; 346(Pt 2): 519-528. | |||||
| REF 40 | The Monoclonal Antibody NEO-201 Enhances Natural Killer Cell Cytotoxicity Against Tumor Cells Through Blockade of the Inhibitory CEACAM5/CEACAM1 Immune Checkpoint Pathway. Cancer Biother Radiopharm. 2020 Apr;35(3):190-198. | |||||
| REF 41 | Clinical pipeline report, company report or official report of Roche. | |||||
| REF 42 | Anticancer Antibodies. (2003) American Journal of Clinical Pathology, 119, 472-485. | |||||
| REF 43 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2836). | |||||
| REF 44 | Binding of Dr adhesins of Escherichia coli to carcinoembryonic antigen triggers receptor dissociation. Mol Microbiol. 2008 Jan;67(2):420-34. | |||||
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