Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT6CQUM)

• DTT Name: B7 homolog 3 (CD276)
• Synonyms: UNQ309/PRO352; PSEC0249; Costimulatory molecule; CD276 antigen; B7H3; B7-H3; 4IgB7H3; 4Ig-B7-H3
• Gene Name: CD276
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Immunoglobulin
• UniProt ID: CD276_HUMAN
• TTD ID: T45612
• Sequence:
  MLRRRGSPGMGVHVGAALGALWFCLTGALEVQVPEDPVVALVGTDATLCCSFSPEPGFSL
  AQLNLIWQLTDTKQLVHSFAEGQDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSF
  TCFVSIRDFGSAAVSLQVAAPYSKPSMTLEPNKDLRPGDTVTITCSSYQGYPEAEVFWQD
  GQGVPLTGNVTTSQMANEQGLFDVHSILRVVLGANGTYSCLVRNPVLQQDAHSSVTITPQ
  RSPTGAVEVQVPEDPVVALVGTDATLRCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFTEG
  RDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPY
  SKPSMTLEPNKDLRPGDTVTITCSSYRGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLF
  DVHSVLRVVLGANGTYSCLVRNPVLQQDAHGSVTITGQPMTFPPEALWVTVGLSVCLIAL
  LVALAFVCWRKIKQSCEEENAGAEDQDGEGEGSKTALQPLKHSDSKEDDGQEIA
• Function: May play a protective role in tumor cells by inhibiting natural-killer mediated cell lysis as well as a role of marker for detection of neuroblastoma cells. May be involved in the development of acute and chronic transplant rejection and in the regulation of lymphocytic activity at mucosal surfaces. Could also play a key role in providing the placenta and fetus with a suitable immunological environment throughout pregnancy. Both isoform 1 and isoform 2 appear to be redundant in their ability to modulate CD4 T-cell responses. Isoform 2 is shown to enhance the induction of cytotoxic T-cells and selectively stimulates interferon gamma production in the presence of T-cell receptor signaling. May participate in the regulation of T-cell-mediated immune response.
• KEGG Pathway: Cell adhesion molecules (CAMs) (hsa04514)

Molecular Interaction Atlas (MIA) of This DTT

11 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
131 I-omburtamab	DM12UX6	Brain and central nervous system tumour	2A00.11	Phase 2/3	[2]
Omburtamab	DMTIESG	Neuroblastoma	2D11.2	Phase 2/3	[3]
Omburtamab I-131	DMPDA17	Neuroblastoma	2D11.2	Phase 2/3	[1]
Enoblituzumab	DMDS20X	Prostate cancer	2C82.0	Phase 2	[4]
TAK-280	DM08RE5	Aggressive cancer	2A00-2F9Z	Phase 2	[5]
DS-7300	DMK4VY9	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[6]
MGC018	DM1KZW0	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[7]
Omburtamab I-124	DMPLBDF	Glioma	2A00.0	Phase 1/2	[1]
124I-8H9	DM5ZC0E	Glioblastoma multiforme	2A00.0	Phase 1	[8]
MGA271	DM2PVLH	Metastatic cancer	2D50-2E2Z	Phase 1	[9]
MGD009	DME4B8I	Solid tumour/cancer	2A00-2F9Z	Phase 1	[4]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Glioma	2C82	Brainstem tissue	3.92E-01	-0.04	-0.81
Glioma	2C82	White matter	7.33E-02	-0.53	-1.33

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] IntraOmmaya compartmental radioimmunotherapy using 131 I-omburtamab-pharmacokinetic modeling to optimize therapeutic index. Eur J Nucl Med Mol Imaging. 2021 Apr;48(4):1166-1177.
• [3] Mast cell proliferation in the cerebrospinal fluid after intraventricular administration of anti-B7H3 immunotherapy. Cancer Immunol Immunother. 2021 Feb 3.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] ClinicalTrials.gov (NCT05220098) A Phase 1/2, First-in-Human, Open-Label, Dose-Escalation Study of TAK-280 in Patients With Unresectable Locally Advanced or Metastatic Cancer. U.S.National Institutes of Health.
• [6] Clinical pipeline report, company report or official report of Daiichi Sankyo.
• [7] Clinical pipeline report, company report or official report of MacroGenics.
• [8] National Cancer Institute Drug Dictionary (drug id 722029).
• [9] T Cell Coinhibition and Immunotherapy in Human Breast Cancer. Discov Med. 2012 October; 14(77): 229-236.