Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Mucin-1 (MUC1)
• Synonyms: Tumour-associated antigen mucin 1; Tumor-associated mucin; Tumor-associated epithelial membraneantigen; Tumor-associated epithelial membrane antigen; Polymorphic epithelial mucin; Peanut-reactive urinary mucin; PUM; PEMT; PEM; MUC-1; Krebs von den Lungen-6; KL-6; H23AG; Episialin; EMA; Carcinoma-associated mucin; Cancer antigen 15-3; CD227 antigen; CD227; CA 15-3; Breast carcinoma-associated antigen DF3
• Gene Name: MUC1
• DTT Type: Clinical trial target; [1]
• UniProt ID: MUC1_HUMAN
• TTD ID: T18779
• Sequence:
  MTPGTQSPFFLLLLLTVLTVVTGSGHASSTPGGEKETSATQRSSVPSSTEKNAVSMTSSV
  LSSHSPGSGSSTTQGQDVTLAPATEPASGSAATWGQDVTSVPVTRPALGSTTPPAHDVTS
  APDNKPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
  APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
  APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
  APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
  APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
  APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
  APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
  APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
  APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
  APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
  APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
  APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
  APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTS
  APDTRPAPGSTAPPAHGVTSAPDTRPAPGSTAPPAHGVTSAPDNRPALGSTAPPVHNVTS
  ASGSASGSASTLVHNGTSARATTTPASKSTPFSIPSHHSDTPTTLASHSTKTDASSTHHS
  SVPPLTSSNHSTSPQLSTGVSFFFLSFHISNLQFNSSLEDPSTDYYQELQRDISEMFLQI
  YKQGGFLGLSNIKFRPGSVVVQLTLAFREGTINVHDVETQFNQYKTEAASRYNLTISDVS
  VSDVPFPFSAQSGAGVPGWGIALLVLVCVLVALAIVYLIALAVCQCRRKNYGQLDIFPAR
  DTYHPMSEYPTYHTHGRYVPPSSTDRSPYEKVSAGNGGSSLSYTNPAVAATSANL
• Function: Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack. The alpha subunit has cell adhesive properties.
• Reactome Pathway:
  Defective C1GALT1C1 causes TNPS (R-HSA-5083632)
  Defective GALNT12 causes CRCS1 (R-HSA-5083636)
  Dectin-2 family (R-HSA-5621480)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  O-linked glycosylation of mucins (R-HSA-913709)
  Termination of O-glycan biosynthesis (R-HSA-977068)
  Defective GALNT3 causes HFTC (R-HSA-5083625)

Molecular Interaction Atlas (MIA) of This DTT

24 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Yttrium (90Y) clivatuzumab tetraxetan	DMOLR5W	Pancreatic cancer	2C10	Phase 3	[1]
TG-4010	DMWE3GB	Bipolar disorder	6A60	Phase 2/3	[2]
AS-1402	DMMX1EJ	Breast cancer	2C60-2C65	Phase 2	[3]
Emepepimut-S	DMCLT2F	Non-small-cell lung cancer	2C25.Y	Phase 2	[4]
GO-203-2c	DMLWKZ7	Acute myeloid leukaemia	2A60	Phase 2	[5]
ICO-25	DMC13BQ	Breast cancer	2C60-2C65	Phase 2	[6]
MUC1-Poly-ICLC	DML7N4B	Colorectal cancer	2B91.Z	Phase 2	[7]
Pankomab-GEX	DMAZ460	Solid tumour/cancer	2A00-2F9Z	Phase 2	[8]
SAR-566658	DMT4FI5	Triple negative breast cancer	2C60-2C65	Phase 2	[9]
Anti-MUC1 CAR T Cells	DM0C1IX	Breast cancer	2C60-2C65	Phase 1/2	[10]
Anti-MUC1 CAR-T cells	DMTQIB2	Colorectal cancer	2B91.Z	Phase 1/2	[11]
BrevaRex	DMCEGP2	Pancreatic cancer	2C10	Phase 1/2	[12]
CAR-T cells targeting Muc1	DM5FKU1	Cervical cancer	2C77.0	Phase 1/2	[13]
CAR-T cells targeting MucI	DMBPN4K	Lung cancer	2C25.0	Phase 1/2	[14]
G0-203-2c	DMG48WN	Pancreatic cancer	2C10	Phase 1/2	[5]
ImMucin	DM09JOZ	Multiple myeloma	2A83	Phase 1/2	[15]
MUC-1 CART cell immunotherapy	DMFUDHM	Intrahepatic cholangiocarcinoma	2C12.10	Phase 1/2	[16]
Muc1-specific gene-engineered T cells	DMPNR0J	Acute myeloid leukaemia	2A60	Phase 1/2	[17]
Anti-MUC1 mab	DMQ5ZND	Pancreatic cancer	2C10	Phase 1	[18]
CART-Muc1 cells	DMOJEXG	Acute myeloid leukaemia	2A60	Phase 1	[19]
HuMNC2-CAR44 T cells	DMVGBA1	Breast cancer	2C60-2C65	Phase 1	[20]
MUC-1 dendritic cancer vaccine	DMG4QDT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[21]
ONT-10	DMUZFVH	Solid tumour/cancer	2A00-2F9Z	Phase 1	[22]
TnMUC-1 CAR-T cell therapy	DMHD6PA	Solid tumour/cancer	2A00-2F9Z	Phase 1	[23]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CAR-T cells targeting Mucl	DMA1BLC	Acute myeloid leukaemia	2A60	Preclinical	[24]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
TG-1031	DM5VJQP	Discovery agent	N.A.	Investigative	[25]

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	1.61E-01	-0.43	-0.83
Lung cancer	2C82	Lung tissue	6.28E-51	-0.72	-1.38
Multiple myeloma	2C82	Bone marrow	1.53E-02	-0.33	-1.54
Bipolar disorder	6A20	Pre-frontal cortex	4.59E-01	-0.07	-0.41
Breast cancer	2C82	Breast tissue	1.85E-53	1.61	1.37
Acute myelocytic leukaemia	2C82	Bone marrow	2.90E-04	0.2	0.38

References

• [1] Clinical pipeline report, company report or official report of Immunomedics.
• [2] A phase II study of Tg4010 (Mva-Muc1-Il2) in association with chemotherapy in patients with stage III/IV Non-small cell lung cancer. J Thorac Oncol. 2008 Jul;3(7):735-44.
• [3] Phase I dose escalation pharmacokinetic assessment of intravenous humanized anti-MUC1 antibody AS1402 in patients with advanced breast cancer. Breast Cancer Res. 2009;11(5):R73.
• [4] Emepepimut-S for non-small cell lung cancer. Expert Opin Biol Ther. 2011 Aug;11(8):1091-7.
• [5] Clinical pipeline report, company report or official report of Genus Oncology.
• [6] The role of epithelial antigens in diagnosis and staging of breast cancer. Arkh Patol. 2002 Nov-Dec;64(6):13-5.
• [7] Early in vivo signaling profiles in MUC1-specific CD4+ T cells responding to two different MUC1-targeting vaccines in two different microenvironments. Oncoimmunology. 2013 Mar 1;2(3):e23429.
• [8] Staining of MUC1 in ovarian cancer tissues with PankoMab-GEX detecting the tumour-associated epitope, TA-MUC1, as compared to antibodies HMFG-1 and 115D8. Histol Histopathol. 2013 Feb;28(2):239-44.
• [9] Integrating in vitro signaling and drug response data from single cell network profiling (SCNP) to inform on individual's AML biology.Molecular Cancer Therapeutics. 11/2011; 10(Supplement 1):A73-A73.
• [10] ClinicalTrials.gov (NCT02587689) Phase I/II Study of Anti-Mucin1 (MUC1) CAR T Cells for Patients With MUC1+ Advanced Refractory Solid Tumor
• [11] ClinicalTrials.gov (NCT02617134) CAR-T Cell Immunotherapy in MUC1 Positive Solid Tumor
• [12] Phase I trial of a murine antibody to MUC1 in patients with metastatic cancer: evidence for the activation of humoral and cellular antitumor immunity. Ann Oncol. 2004 Dec;15(12):1825-33.
• [13] ClinicalTrials.gov (NCT03198052) HER2/Mesothelin/Lewis-Y/PSCA/MUC1/PD-L1/CD80/86-CAR-T Cells Immunotherapy Against Cancers
• [14] ClinicalTrials.gov (NCT03267173) Evaluate the Safety and Efficacy of CAR-T in the Treatment of Pancreatic Cancer.
• [15] Phase I/II study exploring ImMucin, a pan-major histocompatibility complex, anti-MUC1 signal peptide vaccine, in multiple myeloma patients. Br J Haematol. 2015 Apr;169(1):44-56.
• [16] ClinicalTrials.gov (NCT03633773) Safety and Efficacy Evaluation of MUC-1 CART in the Treatment of Intrahepatic Cholangiocarcinoma
• [17] ClinicalTrials.gov (NCT03222674) Multi-CAR T Cell Therapy for Acute Myeloid Leukemia
• [18] Characterization of an anti-MUC1 monoclonal antibody with potential as a cancer vaccine. Hybrid Hybridomics. 2001;20(5-6):313-24.
• [19] ClinicalTrials.gov (NCT03291444) CAR-T Cells Combined With Peptide Specific Dendritic Cell in Relapsed/Refractory Leukemia/MDS
• [20] Clinical pipeline report, company report or official report of Minerva Biotechnologies.
• [21] Dendritic cell vaccine immunotherapy of cancer targeting MUC1 mucin. Int J Mol Med. 2003 Oct;12(4):493-502.
• [22] Clinical pipeline report, company report or official report of Oncothyreon.
• [23] ClinicalTrials.gov (NCT04025216) A Study of CART-TnMUC1 in Patients With TnMUC1-Positive Advanced Cancers. U.S. National Institutes of Health.
• [24] ClinicalTrials.gov (NCT03473457) CAR-T Cells Therapy in Relapsed/Refractory Acute Myeloid Leukemia
• [25] Technology evaluation: TG-1031, Transgene SA.Curr Opin Mol Ther.2000 Feb;2(1):106-11.