Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTY6DTE)

• DTT Name: Carcinoembryonic antigen CEA (CD66e)
• Synonyms: Meconium antigen 100; Carcinoembryonic antigen-related cell adhesion molecule 5; CEA; CD66e antigen
• Gene Name: CEACAM5
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Immunoglobulin
• UniProt ID: CEAM5_HUMAN
• TTD ID: T16601
• Sequence:
  MESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKEVLLLVHNLPQ
  HLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQNIIQNDTGFY
  TLHVIKSDLVNEEATGQFRVYPELPKPSISSNNSKPVEDKDAVAFTCEPETQDATYLWWV
  NNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYKCETQNPVSARRSDSVILNVLYGPDAP
  TISPLNTSYRSGENLNLSCHAASNPPAQYSWFVNGTFQQSTQELFIPNITVNNSGSYTCQ
  AHNSDTGLNRTTVTTITVYAEPPKPFITSNNSNPVEDEDAVALTCEPEIQNTTYLWWVNN
  QSLPVSPRLQLSNDNRTLTLLSVTRNDVGPYECGIQNKLSVDHSDPVILNVLYGPDDPTI
  SPSYTYYRPGVNLSLSCHAASNPPAQYSWLIDGNIQQHTQELFISNITEKNSGLYTCQAN
  NSASGHSRTTVKTITVSAELPKPSISSNNSKPVEDKDAVAFTCEPEAQNTTYLWWVNGQS
  LPVSPRLQLSNGNRTLTLFNVTRNDARAYVCGIQNSVSANRSDPVTLDVLYGPDTPIISP
  PDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAKITPNNNGTYACFVSNL
  ATGRNNSIVKSITVSASGTSPGLSAGATVGIMIGVLVGVALI
• 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.
• Reactome Pathway:
  Cell surface interactions at the vascular wall (R-HSA-202733)
  Post-translational modification (R-HSA-163125)

Molecular Interaction Atlas (MIA) of This DTT

21 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SAR408701	DMXGE3O	Non-small-cell lung cancer	2C25.Y	Phase 3	[2]
Tusamitamab ravtansine	DMMPSA1	Non-small-cell lung cancer	2C25	Phase 3	[3]
CAP1-6D	DMEYIVW	Pancreatic cancer	2C10	Phase 2	[1]
CeaVac	DM6Z9BV	Colorectal cancer	2B91.Z	Phase 2	[4]
GI-6207	DM72O6F	Thyroid cancer	2D10	Phase 2	[5]
IDM-2101	DMABRXY	Colorectal cancer	2B91.Z	Phase 2	[6]
Labetuzumab I-131	DMNO5UE	Colorectal cancer	2B91.Z	Phase 2	[7]
Pentacea	DMGY5JC	Small-cell lung cancer	2C25.Y	Phase 2	[8]
AVX701	DMOPVIQ	Colorectal cancer	2B91.Z	Phase 1/2	[9]
BDC-1001	DMJ5MPG	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[10]
CAR-T cells targeting CEA	DM6VCPX	Colorectal cancer	2B91.Z	Phase 1/2	[11]
CT84.66	DM6078F	Breast cancer	2C60-2C65	Phase 1/2	[12]
123-Iodine-labeled MFE-23	DMCFPX8	Solid tumour/cancer	2A00-2F9Z	Phase 1	[13]
AMG 211	DMA1I04	Solid tumour/cancer	2A00-2F9Z	Phase 1	[14]
Anti-CEA CAR-T cells	DMA7L3O	Acute myeloid leukaemia	2A60	Phase 1	[15]
Anti-CEA-CAR T	DMJA3H1	Colorectal cancer	2B91.Z	Phase 1	[16]
CEA CAR-T	DM45BHM	Ascites	ME04	Phase 1	[17]
CIGB-M3	DMSGRA7	Colorectal cancer	2B91.Z	Phase 1	[18]
MV-CEA	DM1FUAR	Glioblastoma multiforme	2A00.0	Phase 1	[19]
NEO-201	DM830EN	Solid tumour/cancer	2A00-2F9Z	Phase 1	[20]
RG7813	DMACLIH	Solid tumour/cancer	2A00-2F9Z	Phase 1	[21]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
KSB-303	DMMJC4Q	Colorectal cancer	2B91.Z	Discontinued in Phase 1/2	[22]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
HLL1-Fab-A3B3	DM2URWO	Solid tumour/cancer	2A00-2F9Z	Investigative	[23]
ICT-037	DMPH8E9	Solid tumour/cancer	2A00-2F9Z	Investigative	[23]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Breast cancer	2C82	Breast tissue	6.68E-91	0.29	1.07
Thyroid cancer	2C82	Thyroid	6.10E-01	-0.01	-0.03
Glioma	2C82	Brainstem tissue	4.49E-01	-2.02E-03	-0.08
Glioma	2C82	White matter	2.23E-05	-0.56	-2.16
Lung cancer	2C82	Lung tissue	5.59E-43	1.21	1.59
Rectal cancer	2C82	Rectal colon tissue	5.33E-01	0.05	0.51

References

• [1] Identification of an enhancer agonist cytotoxic T lymphocyte peptide from human carcinoembryonic antigen. Cancer Res. 1997 Oct 15;57(20):4570-7.
• [2] ClinicalTrials.gov (NCT02187848) Evaluation of SAR408701 in Patients With Advanced Solid Tumors. U.S. National Institutes of Health.
• [3] 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.
• [4] 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.
• [5] Clinical pipeline report, company report or official report of GlobeImmune.
• [6] 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.
• [7] National Cancer Institute Drug Dictionary (drug id 692828).
• [8] Antibody fragments: Hope and hype. MAbs. 2010 Jan-Feb; 2(1): 77-83.
• [9] Viral vector-based therapeutic cancer vaccines. Cancer J. 2011 Sep-Oct;17(5):359-71.
• [10] Clinical pipeline report, company report or official report of Bolt Biotherapeutics.
• [11] ClinicalTrials.gov (NCT03267173) Evaluate the Safety and Efficacy of CAR-T in the Treatment of Pancreatic Cancer.
• [12] Technology evaluation: cT84.66, City of Hope. Curr Opin Mol Ther. 2004 Feb;6(1):90-5.
• [13] 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.
• [14] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [15] ClinicalTrials.gov (NCT02416466) CAR-T Hepatic Artery Infusions and Sir-Spheres for Liver Metastases
• [16] ClinicalTrials.gov (NCT02349724) A Clinical Research of CAR T Cells Targeting CEA Positive Cancer
• [17] Clinical pipeline report, company report or official report of Sorrento Therapeutics.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] Clinical pipeline report, company report or official report of Roche.
• [22] Anticancer Antibodies. (2003) American Journal of Clinical Pathology, 119, 472-485.
• [23] 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).