Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTV3XPL)

• DTT Name: T-cell surface glycoprotein CD3 gamma (CD3G)
• Synonyms: T3G; T-cell surface glycoprotein CD3 gamma chain; T-cell receptor T3 gamma chain; CD3g
• Gene Name: CD3G
• DTT Type: Clinical trial target; [1]
• UniProt ID: CD3G_HUMAN
• TTD ID: T18972
• Sequence:
  MEQGKGLAVLILAIILLQGTLAQSIKGNHLVKVYDYQEDGSVLLTCDAEAKNITWFKDGK
  MIGFLTEDKKKWNLGSNAKDPRGMYQCKGSQNKSKPLQVYYRMCQNCIELNAATISGFLF
  AEIVSIFVLAVGVYFIAGQDGVRQSRASDKQTLLPNDQLYQPLKDREDDQYSHLQGNQLR
  RN
• Function: When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of downstream signaling pathways. In addition to this role of signal transduction in T-cell activation, CD3G plays an essential role in the dynamic regulation of TCR expression at the cell surface. Indeed, constitutive TCR cycling is dependent on the di-leucine-based (diL) receptor-sorting motif present in CD3G. Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response.
• KEGG Pathway:
  Hematopoietic cell lineage (hsa04640)
  T cell receptor signaling pathway (hsa04660)
  Chagas disease (American trypanosomiasis) (hsa05142)
  Measles (hsa05162)
  HTLV-I infection (hsa05166)
• Reactome Pathway:
  Phosphorylation of CD3 and TCR zeta chains (R-HSA-202427)
  Translocation of ZAP-70 to Immunological synapse (R-HSA-202430)
  Generation of second messenger molecules (R-HSA-202433)
  FCGR activation (R-HSA-2029481)
  Regulation of actin dynamics for phagocytic cup formation (R-HSA-2029482)
  Role of phospholipids in phagocytosis (R-HSA-2029485)
  PD-1 signaling (R-HSA-389948)
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tebentafusp	DMUJ1WV	Gastric cancer	2B72	Approved	[2]
Teplizumab	DMZ3P6C	Type-1 diabetes	5A10	Approved	[1]

5 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ertumaxomab	DM5Z3VP	Breast cancer	2C60-2C65	Phase 2	[3]
MGD007	DMAHWLR	Colorectal cancer	2B91.Z	Phase 1/2	[4]
Autologous T-cell therapy	DMOAET3	Prostate cancer	2C82.0	Phase 1	[5]
MEDI-565	DMFWPLQ	Gastrointestinal cancer	2C11	Phase 1	[4]
MT-110	DMPCUN5	Solid tumour/cancer	2A00-2F9Z	Phase 1	[6]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Trifunctional antibody ertumaxomab: Non-immunological effects on Her2 receptor activity and downstream signaling. MAbs. 2012 Sep-Oct;4(5):614-22.
• [4] Bispecific antibodies rise again. Nat Rev Drug Discov. 2014 Nov;13(11):799-801.
• [5] Antitumor activities of PSMA CD3 diabodies by redirected T-cell lysis of prostate cancer cells. Immunotherapy. 2013 Jan;5(1):27-38.
• [6] 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.