Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Activation B7-1 antigen (CD80)
• Synonyms: T-lymphocyte activation antigen CD80; LAB7; CTLA-4 counter-receptor B7.1; CD28LG1; CD28LG; BB1; B7
• Gene Name: CD80
• DTT Type: Successful target; [1]
• UniProt ID: CD80_HUMAN
• TTD ID: T58238
• Sequence:
  MGHTRRQGTSPSKCPYLNFFQLLVLAGLSHFCSGVIHVTKEVKEVATLSCGHNVSVEELA
  QTRIYWQKEKKMVLTMMSGDMNIWPEYKNRTIFDITNNLSIVILALRPSDEGTYECVVLK
  YEKDAFKREHLAEVTLSVKADFPTPSISDFEIPTSNIRRIICSTSGGFPEPHLSWLENGE
  ELNAINTTVSQDPETELYAVSSKLDFNMTTNHSFMCLIKYGHLRVNQTFNWNTTKQEHFP
  DNLLPSWAITLISVNGIFVICCLTYCFAPRCRERRRNERLRRESVRPV
• Function: T-cell proliferation and cytokine production is induced by the binding of CD28, binding to CTLA-4 has opposite effects and inhibits T-cell activation. Involved in the costimulatory signal essential for T-lymphocyte activation.
• KEGG Pathway:
  Cell adhesion molecules (CAMs) (hsa04514)
  Toll-like receptor signaling pathway (hsa04620)
  Intestinal immune network for IgA production (hsa04672)
  Type I diabetes mellitus (hsa04940)
  Autoimmune thyroid disease (hsa05320)
  Systemic lupus erythematosus (hsa05322)
  Rheumatoid arthritis (hsa05323)
  Allograft rejection (hsa05330)
  Graft-versus-host disease (hsa05332)
  Viral myocarditis (hsa05416)
• Reactome Pathway:
  Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)
  CD28 co-stimulation (R-HSA-389356)
  CD28 dependent PI3K/Akt signaling (R-HSA-389357)
  CD28 dependent Vav1 pathway (R-HSA-389359)
  CTLA4 inhibitory signaling (R-HSA-389513)
  PIP3 activates AKT signaling (R-HSA-1257604)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Abatacept	DMSA8RU	Alopecia areata	ED70.2	Approved	[1]

5 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RhuDex	DMGM1IR	Rheumatoid arthritis	FA20	Phase 2a	[2]
Galiximab	DMTXCUS	Lymphoma	2A80-2A86	Phase 2	[3]
HS-110	DML4RCG	Non-small-cell lung cancer	2C25.Y	Phase 2	[4]
CAR-T cells targeting CD80/86	DM6Z7AD	Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]
MAXY-4	DMMP7XG	Autoimmune diabetes	5A10	Phase 1	[6]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tolerimab	DMZKIE0	Transplant rejection	NE84	Terminated	[7]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Lung cancer	2C82	Lung tissue	6.87E-07	-0.12	-0.3
Rheumatoid arthritis	FA20	Synovial tissue	3.67E-01	0.22	0.55

References

• [1] Selective modulation of T-cell co-stimulation: a novel mode of action for the treatment of rheumatoid arthritis. Clin Exp Rheumatol. 2009 May-Jun;27(3):510-8.
• [2] A phase 1 study of AS1409, a novel antibody-cytokine fusion protein, in patients with malignant melanoma or renal cell carcinoma. Clin Cancer Res. 2011 Apr 1;17(7):1998-2005.
• [3] Phase I/II study of galiximab, an anti-CD80 antibody, for relapsed or refractory follicular lymphoma. J Clin Oncol. 2005 Jul 1;23(19):4390-8.
• [4] Clinical pipeline report, company report or official report of Heat Biologics.
• [5] ClinicalTrials.gov (NCT03198052) HER2/Mesothelin/Lewis-Y/PSCA/MUC1/PD-L1/CD80/86-CAR-T Cells Immunotherapy Against Cancers
• [6] Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science. 2011 Apr 29;332(6029):600-3.
• [7] US patent application no. 2004,0171,123, Albumin fusion proteins.