Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT4RXME)

• DTT Name: Mesothelin (MSLN)
• Synonyms: Prepromegakaryocytepotentiating factor; Pre-pro-megakaryocyte-potentiating factor; Mesothelin, cleaved form; MPF; CAK1 antigen
• Gene Name: MSLN
• DTT Type: Clinical trial target; [1]
• UniProt ID: MSLN_HUMAN
• TTD ID: T87108
• Sequence:
  MALPTARPLLGSCGTPALGSLLFLLFSLGWVQPSRTLAGETGQEAAPLDGVLANPPNISS
  LSPRQLLGFPCAEVSGLSTERVRELAVALAQKNVKLSTEQLRCLAHRLSEPPEDLDALPL
  DLLLFLNPDAFSGPQACTRFFSRITKANVDLLPRGAPERQRLLPAALACWGVRGSLLSEA
  DVRALGGLACDLPGRFVAESAEVLLPRLVSCPGPLDQDQQEAARAALQGGGPPYGPPSTW
  SVSTMDALRGLLPVLGQPIIRSIPQGIVAAWRQRSSRDPSWRQPERTILRPRFRREVEKT
  ACPSGKKAREIDESLIFYKKWELEACVDAALLATQMDRVNAIPFTYEQLDVLKHKLDELY
  PQGYPESVIQHLGYLFLKMSPEDIRKWNVTSLETLKALLEVNKGHEMSPQAPRRPLPQVA
  TLIDRFVKGRGQLDKDTLDTLTAFYPGYLCSLSPEELSSVPPSSIWAVRPQDLDTCDPRQ
  LDVLYPKARLAFQNMNGSEYFVKIQSFLGGAPTEDLKALSQQNVSMDLATFMKLRTDAVL
  PLTVAEVQKLLGPHVEGLKAEERHRPVRDWILRQRQDDLDTLGLGLQGGIPNGYLVLDLS
  MQEALSGTPCLLGPGPVLTVLALLLASTLA
• Function: Membrane-anchored forms may play a role in cellular adhesion.
• Reactome Pathway:
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)
  Post-translational protein phosphorylation (R-HSA-8957275)
  Post-translational modification (R-HSA-163125)

Molecular Interaction Atlas (MIA) of This DTT

28 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CRS-207	DMXU5LZ	Gastric adenocarcinoma	2B72	Phase 2	[2]
MORAb-009	DMCXNIP	Mesothelioma	2C51.2	Phase 2	[1]
Anti-mesothelin CAR transduced PBL	DMXI03L	Cervical cancer	2C77.0	Phase 1/2	[3]
Anti-Mesothelin CAR-T cells	DM4NMBW	Gastric adenocarcinoma	2B72	Phase 1/2	[4]
CAR-T cells targeting Mesothelin	DMMAQJ7	Cervical cancer	2C77.0	Phase 1/2	[5]
CAR-T cells targeting mesothelin	DMPK35H	Pancreatic cancer	2C10	Phase 1/2	[6]
HPN536	DM86OJ0	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[7]
TC-210	DM9S5I1	Cholangiocarcinoma	2C12.10	Phase 1/2	[8]
TC-510	DMSPG60	Breast cancer	2C60-2C65	Phase 1/2	[9]
227Th-labelled MSLN-TTC	DM1ZY6M	Epithelioid mesothelioma	2F10	Phase 1	[10]
Anti-meso-CAR T cells	DMY2MO4	Mesothelin Positive tumour	2C51-2F10	Phase 1	[11]
Anti-meso-CAR vector transduced T cells	DM5UQA9	Endometrial cancer	2C76	Phase 1	[11]
Anti-mesothelin CAR T Cells	DM5BIM1	Tumour	2A00-2F9Z	Phase 1	[12]
ATA2271	DM6O0TM	Mesothelioma	2C51.2	Phase 1	[13]
Autologous T cells transfected with chimeric anti-mesothelin immunoreceptor SS1	DMTLU37	Pancreatic cancer	2C10	Phase 1	[14]
BAY 94-9343	DMCQEL6	Solid tumour/cancer	2A00-2F9Z	Phase 1	[15]
CAR-T Cells targeting Mesothelin	DM6DULC	Pancreatic cancer	2C10	Phase 1	[16]
CAR-T cells targeting Mesothelin	DMTZXSO	Solid tumour/cancer	2A00-2F9Z	Phase 1	[17]
CART-meso cells	DM90QPK	Pancreatic cancer	2C10	Phase 1	[18]
CART-meso-19 T cells	DMZ4I03	Pancreatic cancer	2C10	Phase 1	[19]
CARTmeso/19	DMV84ZR	Pancreatic cancer	2C10	Phase 1	[20]
Hu-CART meso cells	DM9VB4I	Fallopian tube cancer	2C74	Phase 1	[21]
HuCART-meso cells	DM4F8AU	Lymphatic disease	BD9Z	Phase 1	[22]
ICasp9M28z T cell	DMY6V5T	Lung cancer	2C25.0	Phase 1	[23]
MCY-M11	DMAESQI	Fallopian tube cancer	2C74	Phase 1	[24]
Meso-CART	DMQSJ9T	Pancreatic cancer	2C10	Phase 1	[25]
Mesothelin-targeted T cells	DMHXA79	Breast cancer	2C60-2C65	Phase 1	[26]
RG7882	DM2E5Z7	Ovarian cancer	2C73	Phase 1	[27]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SS1(dsFv)-PE38	DM3O4ST	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[28]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ATA3271	DMXQVBT	Mesothelioma	2C51.2	Preclinical	[29]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Pancreatic cancer	2C82	Pancreas	2.86E-20	3.98	6.12
Ovarian cancer	2C82	Ovarian tissue	1.35E-02	5.44	1.92

References

• [1] Phase II clinical trial of amatuximab, a chimeric antimesothelin antibody with pemetrexed and cisplatin in advanced unresectable pleural mesothelioma. Clin Cancer Res. 2014 Dec 1;20(23):5927-36.
• [2] Safety and survival with GVAX pancreas prime and Listeria Monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer. J Clin Oncol. 2015 Apr 20;33(12):1325-33.
• [3] ClinicalTrials.gov (NCT01583686) CAR T Cell Receptor Immunotherapy Targeting Mesothelin for Patients With Metastatic Cancer
• [4] ClinicalTrials.gov (NCT03545815) Study of CRISPR-Cas9 Mediated PD-1 and TCR Gene-knocked Out Mesothelin-directed CAR-T Cells in Patients With Mesothelin Positive Multiple Solid Tumors.
• [5] ClinicalTrials.gov (NCT03356808) Antigen-specific T Cells Against Lung Cancer
• [6] ClinicalTrials.gov (NCT02959151) A Study of Chimeric Antigen Receptor T Cells Combined With Interventional Therapy in Advanced Liver Malignancy
• [7] Clinical pipeline report, company report or official report of Harpoon Therapeutics.
• [8] Clinical pipeline report, company report or official report of TCR2 Therapeutics.
• [9] Clinical pipeline report, company report or official report of TCR2 Therapeutics
• [10] Mesothelin-Targeted Thorium-227 Conjugate (MSLN-TTC): Preclinical Evaluation of a New Targeted Alpha Therapy for Mesothelin-Positive Cancers. Clin Cancer Res. 2019 Aug 1;25(15):4723-4734.
• [11] ClinicalTrials.gov (NCT02580747) Treatment of Relapsed and/or Chemotherapy Refractory Advanced Malignancies by CART-meso
• [12] ClinicalTrials.gov (NCT02930993) Anti-mesothelin CAR T Cells for Patients With Recurrent or Metastatic Malignant Tumors
• [13] Clinical pipeline report, company report or official report of Atara Biotherapeutics.
• [14] ClinicalTrials.gov (NCT01897415) Autologous Redirected RNA Meso CAR T Cells for Pancreatic Cancer
• [15] National Cancer Institute Drug Dictionary (drug id 712853).
• [16] ClinicalTrials.gov (NCT03267173) Evaluate the Safety and Efficacy of CAR-T in the Treatment of Pancreatic Cancer.
• [17] ClinicalTrials.gov (NCT03198052) HER2/Mesothelin/Lewis-Y/PSCA/MUC1/PD-L1/CD80/86-CAR-T Cells Immunotherapy Against Cancers
• [18] ClinicalTrials.gov (NCT03638193) Study of Autologous T-cells in Patients With Metastatic Pancreatic Cancer
• [19] ClinicalTrials.gov (NCT02465983) Pilot Study of Autologous T-cells in Patients With Metastatic Pancreatic Cancer
• [20] ClinicalTrials.gov (NCT03497819) Autologous CARTmeso/19 Against Pancreatic Cancer
• [21] ClinicalTrials.gov (NCT03054298) CAR T Cells in Mesothelin Expressing Cancers
• [22] ClinicalTrials.gov (NCT03323944) CAR T Cell Immunotherapy for Pancreatic Cancer
• [23] ClinicalTrials.gov (NCT02414269) Malignant Pleural Disease Treated With Autologous T Cells Genetically Engineered to Target the Cancer-Cell Surface Antigen Mesothelin
• [24] Clinical pipeline report, company report or official report of MaxCyte.
• [25] ClinicalTrials.gov (NCT02706782) A Study of Mesothelin Redirected Autologous T Cells for Advanced Pancreatic Carcinoma
• [26] ClinicalTrials.gov (NCT02792114) T-Cell Therapy for Advanced Breast Cancer
• [27] Molecular Imaging As a Tool for Drug Development and Trial Design. JCO July 13, 2015 JCO.2015.61.6425
• [28] Mesothelin targeted cancer immunotherapy. Eur J Cancer. 2008 Jan;44(1):46-53.
• [29] Clinical pipeline report, company report or official report of Atara Biotherapeutics.