Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTZ8WH4)

• DTT Name: Tumor-associated calcium signal transducer 1 (EPCAM)
• Synonyms: hEGP314; TROP1; TACSTD1; Major gastrointestinal tumor-associated protein GA733-2; MIC18; M4S1; M1S2; KSA; KS 1/4 antigen; Gastrointestinal carcinoma antigen GA733; GA733-2; Epithelial glycoprotein 314; Epithelial glycoprotein; Epithelial cell surface antigen; Epithelial cell adhesion molecule; Ep-CAM; EGP314; EGP; Cell surface glycoprotein Trop-1; CD326; Adenocarcinoma-associated antigen
• Gene Name: EPCAM
• DTT Type: Clinical trial target; [1]
• UniProt ID: EPCAM_HUMAN
• TTD ID: T47863
• Sequence:
  MAPPQVLAFGLLLAAATATFAAAQEECVCENYKLAVNCFVNNNRQCQCTSVGAQNTVICS
  KLAAKCLVMKAEMNGSKLGRRAKPEGALQNNDGLYDPDCDESGLFKAKQCNGTSMCWCVN
  TAGVRRTDKDTEITCSERVRTYWIIIELKHKAREKPYDSKSLRTALQKEITTRYQLDPKF
  ITSILYENNVITIDLVQNSSQKTQNDVDIADVAYYFEKDVKGESLFHSKKMDLTVNGEQL
  DLDPGQTLIYYVDEKAPEFSMQGLKAGVIAVIVVVVIAVVAGIVVLVISRKKRMAKYEKA
  EIKEMGEMHRELNA
• Function: Plays a role in embryonic stem cells proliferation and differentiation. Up-regulates the expression of FABP5, MYC and cyclins A and E. May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as a first line of defense against mucosal infection.
• Reactome Pathway: Cell surface interactions at the vascular wall (R-HSA-202733)

Molecular Interaction Atlas (MIA) of This DTT

9 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Vicineum	DMLO0KD	Bladder cancer	2C94	Phase 3	[2]
VB4-845	DMGKRAJ	Head and neck cancer	2D42	Phase 2/3	[1]
CAR-T Cells targeting EpCAM	DMREQCF	Colon cancer	2B90.Z	Phase 1/2	[3]
A-337	DMRWTFG	Non-small-cell lung cancer	2C25.Y	Phase 1	[4]
CAR-T cells recognizing EpCAM	DMC7Y5F	Breast cancer	2C60-2C65	Phase 1	[5]
Citatuzumab bogatox	DMRJF2Q	Solid tumour/cancer	2A00-2F9Z	Phase 1	[6]
ING-1	DM5WCBM	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
MT-110	DMPCUN5	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]
EPCAM-targeted CAR-T cells	DMV6RMB	Gastric adenocarcinoma	2B72	Clinical trial	[9]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
IGN-101	DMOG1LX	Colorectal cancer	2B91.Z	Discontinued in Phase 2	[10]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Rectal cancer	2C82	Rectal colon tissue	5.99E-02	-0.11	-1.11
Head and neck cancer	2C82	Head and neck tissue	6.19E-04	-1.01	-0.49

References

• [1] A bispecific EpCAM/CD133 targeted toxin is effective against carcinoma. Target Oncol. 2014 September; 9(3): 239-249.
• [2] Clinical pipeline report, company report or official report of Sesen Bio.
• [3] ClinicalTrials.gov (NCT03563326) Intraperitoneal Infusion of EpCAM CAR-T Cell in Advanced Gastric Cancer With Peritoneal Metastasis (WCH-GC-CART)
• [4] Bispecific antibodies: a mechanistic review of the pipeline. Nat Rev Drug Discov. 2019 Aug;18(8):585-608.
• [5] ClinicalTrials.gov (NCT02915445) EpCAM CAR-T for Treatment of Nasopharyngeal Carcinoma and Breast Cancer
• [6] Preclinical evaluation of VB6-845: an anti-EpCAM immunotoxin with reduced immunogenic potential. Cancer Biother Radiopharm. 2012 Nov;27(9):582-92.
• [7] ING-1, a monoclonal antibody targeting Ep-CAM in patients with advanced adenocarcinomas. Clin Cancer Res. 2004 Nov 15;10(22):7555-65.
• [8] EpCAM/CD3-Bispecific T-cell engaging antibody MT110 eliminates primary human pancreatic cancer stem cells. Clin Cancer Res. 2012 Jan 15;18(2):465-74.
• [9] ClinicalTrials.gov (NCT02725125) Study Evaluating the Efficacy and Safety With CAR-T for Stomach Cancer
• [10] Drug evaluation: IGN-101--an anti-EpCAM murine antibody vaccine for cancer. Curr Opin Mol Ther. 2006 Aug;8(4):358-65.