Target General Infomation
Target ID
T64969 (Former ID: TTDR00576)
Target Name
Epidermal growth factor receptor variant III (EGFR vIII)
Synonyms
ERBB1 variant III; ERBB variant III
Gene Name
EGFR
Target Type
Clinical trial target
[1]
Disease [+] 4 Target-related Diseases +
1 Brain cancer [ICD-11: 2A00]
2 Liver cancer [ICD-11: 2C12]
3 Lung cancer [ICD-11: 2C25]
4 Pancreatic cancer [ICD-11: 2C10]
Function
Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin. Plays a role in enhancing learning and memory performance (By similarity).
BioChemical Class
Kinase
UniProt ID
EGFR_HUMAN
EC Number
EC 2.7.10.1
Sequence
MRPSGTAGAALLALLAALCPASRALEEKKVCQGTSNKLTQLGTFEDHFLSLQRMFNNCEV
VLGNLEITYVQRNYDLSFLKTIQEVAGYVLIALNTVERIPLENLQIIRGNMYYENSYALA
VLSNYDANKTGLKELPMRNLQEILHGAVRFSNNPALCNVESIQWRDIVSSDFLSNMSMDF
QNHLGSCQKCDPSCPNGSCWGAGEENCQKLTKIICAQQCSGRCRGKSPSDCCHNQCAAGC
TGPRESDCLVCRKFRDEATCKDTCPPLMLYNPTTYQMDVNPEGKYSFGATCVKKCPRNYV
VTDHGSCVRACGADSYEMEEDGVRKCKKCEGPCRKVCNGIGIGEFKDSLSINATNIKHFK
NCTSISGDLHILPVAFRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAWPENRTDLHAF
ENLEIIRGRTKQHGQFSLAVVSLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKL
FGTSGQKTKIISNRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCN
LLEGEPREFVENSECIQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVM
GENNTLVWKYADAGHVCHLCHPNCTYGCTGPGLEGCPTNGPKIPSIATGMVGALLLLLVV
ALGIGLFMRRRHIVRKRTLRRLLQERELVEPLTPSGEAPNQALLRILKETEFKKIKVLGS
GAFGTVYKGLWIPEGEKVKIPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGI
CLTSTVQLITQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAA
RNVLVKTPQHVKITDFGLAKLLGAEEKEYHAEGGKVPIKWMALESILHRIYTHQSDVWSY
GVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYMIMVKCWMIDADSRPK
FRELIIEFSKMARDPQRYLVIQGDERMHLPSPTDSNFYRALMDEEDMDDVVDADEYLIPQ
QGFFSSPSTSRTPLLSSLSATSNNSTVACIDRNGLQSCPIKEDSFLQRYSSDPTGALTED
SIDDTFLPVPEYINQSVPKRPAGSVQNPVYHNQPLNPAPSRDPHYQDPHSTAVGNPEYLN
TVQPTCVNSTFDSPAHWAQKGSHQISLDNPDYQQDFFPKEAKPNGIFKGSTAENAEYLRV
APQSSEFIGA
Drugs and Modes of Action
Clinical Trial Drug(s) [+] 9 Clinical Trial Drugs +
1 Anti-EGFR V III CAR-T cells Drug Info Phase 1/2 Glioma [2]
2 Anti-EGFRvIII CAR transduced PBL Drug Info Phase 1/2 Brain cancer [1]
3 EGFRvIII CAR Drug Info Phase 1/2 Glioblastoma multiforme [1]
4 Anti-EGFRvIII CAR T cells Drug Info Phase 1 Glioblastoma multiforme [3]
5 CAR-T Cells targeting EGFRvIII Drug Info Phase 1 Pancreatic cancer [4]
6 CAR-T cells targeting EGFRviii Drug Info Phase 1 Glioblastoma multiforme [5]
7 CART-EGFRvIII T cells Drug Info Phase 1 Recurrent glioblastoma [6]
8 EGFRvIII CAR T cells Drug Info Phase 1 Glioblastoma multiforme [7]
9 EGFRvIII-CARs Drug Info Phase 1 Recurrent glioblastoma [8]
Mode of Action [+] 2 Modes of Action +
CAR-T-Cell-Therapy [+] 8 CAR-T-Cell-Therapy drugs +
1 Anti-EGFRvIII CAR transduced PBL Drug Info [1]
2 Anti-EGFR V III CAR-T cells Drug Info [2]
3 Anti-EGFRvIII CAR T cells Drug Info [3]
4 CAR-T Cells targeting EGFRvIII Drug Info [4]
5 CAR-T cells targeting EGFRviii Drug Info [5]
6 CART-EGFRvIII T cells Drug Info [6], [10]
7 EGFRvIII CAR T cells Drug Info [7]
8 EGFRvIII-CARs Drug Info [8]
Modulator [+] 1 Modulator drugs +
1 EGFRvIII CAR Drug Info [9]
References
REF 1 ClinicalTrials.gov (NCT01454596) CAR T Cell Receptor Immunotherapy Targeting EGFRvIII for Patients With Malignant Gliomas Expressing EGFRvIII. U.S. National Institutes of Health.
REF 2 ClinicalTrials.gov (NCT03638206) Autologous CAR-T/TCR-T Cell Immunotherapy for Malignancies
REF 3 ClinicalTrials.gov (NCT02844062) Pilot Study of Autologous Anti-EGFRvIII CAR T Cells in Recurrent Glioblastoma Multiforme
REF 4 ClinicalTrials.gov (NCT03267173) Evaluate the Safety and Efficacy of CAR-T in the Treatment of Pancreatic Cancer.
REF 5 ClinicalTrials.gov (NCT03170141) Immunogene-modified T (IgT) Cells Against Glioblastoma Multiforme
REF 6 ClinicalTrials.gov (NCT03726515) CART-EGFRvIII + Pembrolizumab in GBM
REF 7 ClinicalTrials.gov (NCT02664363) EGFRvIII CAR T Cells for Newly-Diagnosed WHO Grade IV Malignant Glioma
REF 8 ClinicalTrials.gov (NCT03283631) Intracerebral EGFR-vIII CAR-T Cells for Recurrent GBM
REF 9 EGFRvIII mCAR-modified T-cell therapy cures mice with established intracerebral glioma and generates host immunity against tumor-antigen loss. Clin Cancer Res. 2014 Feb 15;20(4):972-84.
REF 10 ClinicalTrials.gov (NCT02209376) Autologous T Cells Redirected to EGFRVIII-With a Chimeric Antigen Receptor in Patients With EGFRVIII+ Glioblastoma

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